Microvascular research最新文献_第3页

Quantitative evaluation of retinal vascular morphology based on the human visual bionic mechanism for the evaluation of diabetic retinopathy onset 基于人眼视觉仿生机制的视网膜血管形态定量评价对糖尿病视网膜病变发病的评价

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-03-01 Epub Date: 2026-01-06 DOI: 10.1016/j.mvr.2026.104901

Yi Xu , Yuting Wu , Saiguang Ling , Zhou Dong , Xin Ke , Lina Lu , Zheng Ye , Jianling Song , Haidong Zou

Background and aims

A limited amount of diabetic retinopathy (DR) development can be explained by traditional risk factors. This study aimed to determine the association of artificial intelligence (AI)-assisted retinal vasculature measurement parameters with DR onset in adults with type 2 diabetes.

Methods

This observational cohort study was conducted in 556 patients with type 2 diabetes without DR who underwent general and ophthalmological examinations. Their blood pressure, body mass index (BMI), fasting blood glucose (FBG), and glycosylated hemoglobin levels were measured. An AI-based fundus image analysis system was used to assess vessel tortuosity, fractal dimension, and retinal arteriolar/venular diameters in different regions.

Results

At the end of the observation period, 299 patients remained free of DR (control group), whereas 257 developed DR (progression group). The retinal arteriolar caliber, venular caliber, arteriolar tortuosity, and venular tortuosity did not differ significantly between the groups at baseline (P > 0.05). However, DR onset was significantly correlated with retinal arteriolar caliber, fractal dimensions, and retinal venular tortuosity (P < 0.05). The widening of the retinal arteriolar diameter within the 1.5–2.0 PD region of the optical disc center was the strongest predictor of DR development. It also improved the performance of the DR onset prediction model compared with those using traditional risk factors alone.

Conclusions

AI-assisted retinal vasculature measurements were associated with DR onset and progression. In addition to increased retinal venular tortuosity and fractal dimension, retinal arteriolar caliber within the 1.5–2.0 PD may serve as a valuable biomarker of early vascular dysfunction and increased DR risk.

背景与目的：传统的危险因素可以解释少量糖尿病视网膜病变（DR）的发生。本研究旨在确定人工智能（AI）辅助视网膜血管测量参数与成人2型糖尿病患者DR发病的关系。方法对556例无DR的2型糖尿病患者进行了观察性队列研究。测量他们的血压、体重指数（BMI）、空腹血糖（FBG）和糖化血红蛋白水平。采用基于人工智能的眼底图像分析系统对不同区域的血管弯曲度、分形维数和视网膜小静脉直径进行评估。结果观察结束时，299例患者未发生DR（对照组），257例患者发生DR（进展组）。各组视网膜小动脉口径、静脉口径、小动脉迂曲度和静脉迂曲度在基线时无显著差异（P > 0.05）。然而，DR的发病与视网膜小动脉直径、分形维数和视网膜小静脉弯曲度有显著相关（P < 0.05）。在光盘中心1.5-2.0 PD区域内视网膜小动脉直径的扩大是DR发展的最强预测因子。与仅使用传统危险因素的预测模型相比，该方法还提高了DR发病预测模型的性能。结论人工智能辅助视网膜血管测量与DR的发生和进展有关。除了视网膜静脉曲度和分形维数增加外，1.5-2.0 PD内的视网膜小动脉直径可能是早期血管功能障碍和DR风险增加的有价值的生物标志物。

{"title":"Quantitative evaluation of retinal vascular morphology based on the human visual bionic mechanism for the evaluation of diabetic retinopathy onset","authors":"Yi Xu , Yuting Wu , Saiguang Ling , Zhou Dong , Xin Ke , Lina Lu , Zheng Ye , Jianling Song , Haidong Zou","doi":"10.1016/j.mvr.2026.104901","DOIUrl":"10.1016/j.mvr.2026.104901","url":null,"abstract":"<div><h3>Background and aims</h3><div>A limited amount of diabetic retinopathy (DR) development can be explained by traditional risk factors. This study aimed to determine the association of artificial intelligence (AI)-assisted retinal vasculature measurement parameters with DR onset in adults with type 2 diabetes.</div></div><div><h3>Methods</h3><div>This observational cohort study was conducted in 556 patients with type 2 diabetes without DR who underwent general and ophthalmological examinations. Their blood pressure, body mass index (BMI), fasting blood glucose (FBG), and glycosylated hemoglobin levels were measured. An AI-based fundus image analysis system was used to assess vessel tortuosity, fractal dimension, and retinal arteriolar/venular diameters in different regions.</div></div><div><h3>Results</h3><div>At the end of the observation period, 299 patients remained free of DR (control group), whereas 257 developed DR (progression group). The retinal arteriolar caliber, venular caliber, arteriolar tortuosity, and venular tortuosity did not differ significantly between the groups at baseline (<em>P</em> > 0.05). However, DR onset was significantly correlated with retinal arteriolar caliber, fractal dimensions, and retinal venular tortuosity (<em>P</em> < 0.05). The widening of the retinal arteriolar diameter within the 1.5–2.0 PD region of the optical disc center was the strongest predictor of DR development. It also improved the performance of the DR onset prediction model compared with those using traditional risk factors alone.</div></div><div><h3>Conclusions</h3><div>AI-assisted retinal vasculature measurements were associated with DR onset and progression. In addition to increased retinal venular tortuosity and fractal dimension, retinal arteriolar caliber within the 1.5–2.0 PD may serve as a valuable biomarker of early vascular dysfunction and increased DR risk.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104901"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of the menstrual cycle phase on microvascular function at high altitude 高海拔地区月经周期阶段对微血管功能的影响。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-03-01 Epub Date: 2025-12-13 DOI: 10.1016/j.mvr.2025.104898

Guia Tagliapietra , Giorgio Manferdelli , Tom Citherlet , Antoine Raberin , Benjamin J. Narang , Tadej Debevec , Grégoire P. Millet

Ovarian hormones may modulate key physiological functions that play a crucial role in the acute response to hypoxia. Women remain underrepresented in high-altitude physiology research. This exploratory study aimed to investigate the impact of menstrual cycle (MC) phases on resting skeletal muscle oxygen consumption and post-occlusive microvascular reactive hyperemia in the lower limbs during acute high-altitude exposure in eumenorrheic women. Microvascular function was assessed via vascular occlusion test in combination with near-infrared spectroscopy on the vastus lateralis muscle. Measurements were conducted at low altitude (1224 m) and after one night at 3375 m (inspired O₂ pressure: 96 ± 1 mmHg) during both the early follicular (EF) and mid-luteal (ML) phases. At high altitude, baseline tissue saturation index (TSI) (65.0 ± 4.8 vs. 66.1 ± 2.7 %; p = 0.559), desaturation rate (−0.086 ± 0.061 vs. −0.080 ± 0.039 %·s⁻¹; p = 0.920), normalized reperfusion slope (0.013 ± 0.010 vs. 0.014 ± 0.005 %·s⁻¹; p = 0.100) and minimum TSI (52.9 ± 6.8 vs. 53.9 ± 3.9 %; p = 0.647) did not differ significantly between EF and ML. Reperfusion rate decreased significantly from low (0.894 ± 0.320) to high altitude during both EF (0.661 ± 0.424; p = 0.027) and ML (0.722 ± 0.253; p = 0.027). These findings suggest that microvascular function is not significantly modulated by the MC at 3375 m. This study adds further evidence suggesting that no specific recommendation regarding the optimal menstrual cycle phase for acute high-altitude exposure is warranted.

卵巢激素可能调节在缺氧急性反应中起关键作用的关键生理功能。女性在高海拔生理学研究中的代表性仍然不足。本探索性研究旨在探讨月经周期（MC）阶段对急性高海拔暴露绝经期女性下肢静息骨骼肌耗氧量和闭塞后微血管反应性充血的影响。通过血管闭塞试验结合近红外光谱对股外侧肌进行微血管功能评估。在低海拔（1224 m）和3375 m（吸气O2压：96 ± 1 mmHg）一晚后，在卵泡早期（EF）和黄体中期（ML）阶段进行测量。在高海拔,基线组织饱和指数(TSI)(65.0 ±  4.8和66.1±2.7  %;p = 0.559),稀释率(-0.086 ±  0.061和-0.080±0.039  %·s - 1; p = 0.920),归一化再灌注斜率( 0.013±0.010 vs 0.014  ±0.005  %·s - 1; p = 0.100)和最小TSI( 52.9±6.8 vs 53.9  ±3.9  %;p = 0.647)EF和毫升之间没有显著差异。再灌注率显著降低从低(0.894 ±0.320 )在EF(高海拔0.661 ± 0.424;p = 0.027)和ML（0.722±0.253;p = 0.027）。这些发现表明，在3375 m处，微血管功能不受MC的显著调节。这项研究提供了进一步的证据，表明没有关于急性高海拔暴露的最佳月经周期的具体建议是必要的。

{"title":"Impact of the menstrual cycle phase on microvascular function at high altitude","authors":"Guia Tagliapietra , Giorgio Manferdelli , Tom Citherlet , Antoine Raberin , Benjamin J. Narang , Tadej Debevec , Grégoire P. Millet","doi":"10.1016/j.mvr.2025.104898","DOIUrl":"10.1016/j.mvr.2025.104898","url":null,"abstract":"<div><div>Ovarian hormones may modulate key physiological functions that play a crucial role in the acute response to hypoxia. Women remain underrepresented in high-altitude physiology research. This exploratory study aimed to investigate the impact of menstrual cycle (MC) phases on resting skeletal muscle oxygen consumption and post-occlusive microvascular reactive hyperemia in the lower limbs during acute high-altitude exposure in eumenorrheic women. Microvascular function was assessed via vascular occlusion test in combination with near-infrared spectroscopy on the <em>vastus lateralis</em> muscle. Measurements were conducted at low altitude (1224 m) and after one night at 3375 m (inspired O<sub>2</sub> pressure: 96 ± 1 mmHg) during both the early follicular (EF) and mid-luteal (ML) phases. At high altitude, baseline tissue saturation index (TSI) (65.0 ± 4.8 vs. 66.1 ± 2.7 %; <em>p</em> = 0.559), desaturation rate (−0.086 ± 0.061 vs. −0.080 ± 0.039 %·s<sup>−1</sup>; <em>p</em> = 0.920), normalized reperfusion slope (0.013 ± 0.010 vs. 0.014 ± 0.005 %·s<sup>−1</sup>; <em>p</em> = 0.100) and minimum TSI (52.9 ± 6.8 vs. 53.9 ± 3.9 %; <em>p</em> = 0.647) did not differ significantly between EF and ML. Reperfusion rate decreased significantly from low (0.894 ± 0.320) to high altitude during both EF (0.661 ± 0.424; <em>p</em> = 0.027) and ML (0.722 ± 0.253; <em>p</em> = 0.027). These findings suggest that microvascular function is not significantly modulated by the MC at 3375 m. This study adds further evidence suggesting that no specific recommendation regarding the optimal menstrual cycle phase for acute high-altitude exposure is warranted.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104898"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The underdiagnosed risk of Coronary microvascular dysfunction in post CABG/angioplasty patients a call for myocardial perfusion mapping of blood flow dynamics 冠脉搭桥/血管成形术后患者冠状动脉微血管功能障碍未被诊断的风险呼吁对血流动力学进行心肌灌注测绘。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-03-01 Epub Date: 2025-11-26 DOI: 10.1016/j.mvr.2025.104886

B. Gayathri , K. Sreekanth , G. Aparna , C. Chandana , N. Radhakrishnan , E.K. Radhakrishnan

Angioplasty and coronary artery bypass grafting (CABG) are common interventions for the management of coronary artery disease aiming to address atherosclerotic plaques in the epicardial coronary arteries. However, many patients experience recurrent angina and other complications such as low cardiac output and even mortality due to other undiagnosed pathologies. Coronary microvascular dysfunction (CMD), which causes impaired blood flow in the microvascular network is a critically overlooked factor in this regard. Such microvascular dysfunction occurs due to the endothelial abnormalities leading to vascular remodelling, and increased resistance to blood flow. The mobilization of unstable plaques during operative procedures such as stenting, angioplasty, and bypass surgery can also contribute to the microcirculatory obstruction, potentially resulting in fatal coronary embolization. Also, such plaque rupture release emboli that can migrate and obstruct the distal arterioles, resulting in low cardiac output, recurrent angina, and ischemia. These microvascular blocks resulting from preexisting dysfunction or iatrogenic embolization are mostly undiagnosed after a CABG or angioplasty. Diagnosis of CMD is challenging, as conventional imaging techniques only focus on macrovascular assessment, neglecting the importance of microvascular hemodynamics. Current diagnostic protocols need a re-evaluation to include methods to assess microvascular perfusion dynamics in postoperative patients.

血管成形术和冠状动脉旁路移植术（CABG）是治疗冠状动脉疾病的常见干预措施，旨在解决心外膜冠状动脉粥样硬化斑块。然而，许多患者会经历复发性心绞痛和其他并发症，如低心输出量，甚至由于其他未确诊的病理而死亡。冠状动脉微血管功能障碍（CMD）会导致微血管网络中的血流受损，这是一个被严重忽视的因素。这种微血管功能障碍的发生是由于内皮异常导致血管重构，血流阻力增加。在支架置入术、血管成形术和搭桥手术等手术过程中，不稳定斑块的动员也可能导致微循环阻塞，可能导致致命的冠状动脉栓塞。此外，斑块破裂释放出栓塞，栓塞可迁移并阻塞远端小动脉，导致心排血量低、心绞痛复发和缺血。这些由先前存在的功能障碍或医源性栓塞引起的微血管阻塞在冠脉搭桥或血管成形术后大多无法诊断。CMD的诊断具有挑战性，因为传统的成像技术只关注大血管的评估，而忽视了微血管血流动力学的重要性。目前的诊断方案需要重新评估，包括评估术后患者微血管灌注动力学的方法。

{"title":"The underdiagnosed risk of Coronary microvascular dysfunction in post CABG/angioplasty patients a call for myocardial perfusion mapping of blood flow dynamics","authors":"B. Gayathri , K. Sreekanth , G. Aparna , C. Chandana , N. Radhakrishnan , E.K. Radhakrishnan","doi":"10.1016/j.mvr.2025.104886","DOIUrl":"10.1016/j.mvr.2025.104886","url":null,"abstract":"<div><div>Angioplasty and coronary artery bypass grafting (CABG) are common interventions for the management of coronary artery disease aiming to address atherosclerotic plaques in the epicardial coronary arteries. However, many patients experience recurrent angina and other complications such as low cardiac output and even mortality due to other undiagnosed pathologies. Coronary microvascular dysfunction (CMD), which causes impaired blood flow in the microvascular network is a critically overlooked factor in this regard. Such microvascular dysfunction occurs due to the endothelial abnormalities leading to vascular remodelling, and increased resistance to blood flow. The mobilization of unstable plaques during operative procedures such as stenting, angioplasty, and bypass surgery can also contribute to the microcirculatory obstruction, potentially resulting in fatal coronary embolization. Also, such plaque rupture release emboli that can migrate and obstruct the distal arterioles, resulting in low cardiac output, recurrent angina, and ischemia. These microvascular blocks resulting from preexisting dysfunction or iatrogenic embolization are mostly undiagnosed after a CABG or angioplasty. Diagnosis of CMD is challenging, as conventional imaging techniques only focus on macrovascular assessment, neglecting the importance of microvascular hemodynamics. Current diagnostic protocols need a re-evaluation to include methods to assess microvascular perfusion dynamics in postoperative patients.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104886"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erythrocyte rheology under anesthesia: Insights from glycated and non-glycated red blood cells 麻醉下的红细胞流变学：糖化和非糖化红细胞的观察。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-03-01 Epub Date: 2025-12-22 DOI: 10.1016/j.mvr.2025.104900

Marcus V. Batista da Silva , Horacio V. Castellini , Nicolás A. Alet , Bibiana D. Riquelme , Analía I. Alet

Hemorheological alterations in diabetes mellitus complicate surgical outcomes. This study investigated the rheological effects of commonly used anesthetic drugs (propofol, remifentanil, vecuronium, and their combinations) on healthy human erythrocytes and on glycated erythrocytes in vitro to simulate diabetic hyperglycemia. Experiments were performed using an erythrocyte rheometer, an optical aggregometer, and digital image analysis. The results demonstrate that these anesthetic drugs increase erythrocyte aggregation. Propofol and its combinations showed a possible synergistic effect, resulting in the formation of larger aggregates. Viscoelasticity analysis of non-glycated erythrocytes showed that propofol alone increased the elastic modulus. Conversely, the combination of propofol, remifentanil, and vecuronium decreased the erythrocyte stationary storage modulus, suggesting possible interactions with the cytoskeleton and lipid bilayer. In glycated erythrocytes, the same drug combinations did not significantly affect viscoelastic parameters. These findings indicate that these drugs, when evaluated at clinically relevant concentrations, affect hemorheological parameters differently in non-glycated and glycated erythrocytes. These results provide information that could help in understanding microvascular complications in diabetic patients during and after surgical procedures.

糖尿病患者的血液流变学改变使手术结果复杂化。本研究研究了常用麻醉药物（异丙酚、瑞芬太尼、维库溴铵及其联合用药）对体外模拟糖尿病高血糖的健康人红细胞和糖化红细胞的流变学影响。实验使用红细胞流变仪、光学聚集仪和数字图像分析进行。结果表明，这些麻醉药物增加红细胞聚集。异丙酚及其组合可能表现出协同效应，导致形成更大的聚集体。非糖化红细胞的粘弹性分析表明，单独使用异丙酚可增加红细胞的弹性模量。相反，异丙酚、瑞芬太尼和维库溴铵联合使用会降低红细胞固定储存模量，提示可能与细胞骨架和脂质双分子层相互作用。在糖化红细胞中，相同的药物组合对粘弹性参数没有显著影响。这些发现表明，在临床相关浓度下，这些药物对非糖化红细胞和糖化红细胞的血液流变学参数的影响不同。这些结果提供了有助于了解糖尿病患者手术期间和手术后微血管并发症的信息。

{"title":"Erythrocyte rheology under anesthesia: Insights from glycated and non-glycated red blood cells","authors":"Marcus V. Batista da Silva , Horacio V. Castellini , Nicolás A. Alet , Bibiana D. Riquelme , Analía I. Alet","doi":"10.1016/j.mvr.2025.104900","DOIUrl":"10.1016/j.mvr.2025.104900","url":null,"abstract":"<div><div>Hemorheological alterations in diabetes mellitus complicate surgical outcomes. This study investigated the rheological effects of commonly used anesthetic drugs (propofol, remifentanil, vecuronium, and their combinations) on healthy human erythrocytes and on glycated erythrocytes <em>in vitro</em> to simulate diabetic hyperglycemia. Experiments were performed using an erythrocyte rheometer, an optical aggregometer, and digital image analysis. The results demonstrate that these anesthetic drugs increase erythrocyte aggregation. Propofol and its combinations showed a possible synergistic effect, resulting in the formation of larger aggregates. Viscoelasticity analysis of non-glycated erythrocytes showed that propofol alone increased the elastic modulus. Conversely, the combination of propofol, remifentanil, and vecuronium decreased the erythrocyte stationary storage modulus, suggesting possible interactions with the cytoskeleton and lipid bilayer. In glycated erythrocytes, the same drug combinations did not significantly affect viscoelastic parameters. These findings indicate that these drugs, when evaluated at clinically relevant concentrations, affect hemorheological parameters differently in non-glycated and glycated erythrocytes. These results provide information that could help in understanding microvascular complications in diabetic patients during and after surgical procedures.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104900"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pericytes at the crossroads of sepsis: Mechanisms and therapeutic opportunities in vascular barrier dysfunction 脓毒症的十字路口周细胞：血管屏障功能障碍的机制和治疗机会

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-03-01 Epub Date: 2025-12-03 DOI: 10.1016/j.mvr.2025.104895

Changhong Miao , Lu Xiao , Xinyi Xu , Jingchao Miao , Jiajin Liu , Haobo Zhao

This review highlights the crucial role of pericytes in sepsis-induced vascular barrier dysfunction and proposes pericytes as a potential therapeutic target. Research shows that the loss of pericytes is closely associated with increased microvascular permeability, abnormal microcirculation, and multi-organ dysfunction in sepsis. Interventions such as activation of the Ang/Tie2 pathway, VEGF inhibition, PDGF-B signaling modulation, and MSC-derived exosomes may effectively restore microvascular stability and alleviate organ damage related to sepsis. The article further explores the integration of cutting-edge technologies such as single-cell genomics and proteomics to precisely identify pericyte function and therapeutic targets, providing new directions and innovative strategies for sepsis treatment.

Background

Pericytes are mural cells embedded in the vascular basement membrane and form an integral part of the microvascular structure. Through close interactions with endothelial cells, they participate in vascular remodeling, maintenance of barrier integrity, regulation of capillary blood flow, and protection of the central nervous system. Relevant studies have increasingly emphasized the role of pericytes in sepsis-associated microcirculatory dysfunction, suggesting new directions for therapeutic intervention. This review outlines the biological features of pericytes and their contribution to sepsis-related vascular pathology, with particular attention to mechanisms by which pericytes mediate organ injury. By highlighting key signaling pathways and processes involved in pericyte-driven vascular barrier disruption, we suggest that targeting pericytes may offer a potential strategy for the treatment of sepsis.

这篇综述强调了周细胞在脓毒症诱导的血管屏障功能障碍中的重要作用，并提出周细胞是一个潜在的治疗靶点。研究表明，脓毒症中周细胞的丢失与微血管通透性增高、微循环异常、多器官功能障碍密切相关。激活Ang/Tie2通路、抑制VEGF、PDGF-B信号调节和msc衍生外泌体等干预措施可有效恢复微血管稳定性，减轻败血症相关器官损伤。本文进一步探讨了单细胞基因组学和蛋白质组学等前沿技术的融合，以精确识别周细胞功能和治疗靶点，为脓毒症的治疗提供新的方向和创新策略。周细胞是嵌入血管基底膜的壁细胞，是微血管结构的组成部分。它们通过与内皮细胞的密切相互作用，参与血管重塑，维持屏障完整性，调节毛细血管血流，保护中枢神经系统。相关研究越来越强调周细胞在脓毒症相关微循环功能障碍中的作用，为治疗干预提供了新的方向。本文概述了周细胞的生物学特征及其在脓毒症相关血管病理学中的作用，并特别关注周细胞介导器官损伤的机制。通过强调周细胞驱动的血管屏障破坏的关键信号通路和过程，我们建议靶向周细胞可能为脓毒症的治疗提供一种潜在的策略。

{"title":"Pericytes at the crossroads of sepsis: Mechanisms and therapeutic opportunities in vascular barrier dysfunction","authors":"Changhong Miao , Lu Xiao , Xinyi Xu , Jingchao Miao , Jiajin Liu , Haobo Zhao","doi":"10.1016/j.mvr.2025.104895","DOIUrl":"10.1016/j.mvr.2025.104895","url":null,"abstract":"<div><div>This review highlights the crucial role of pericytes in sepsis-induced vascular barrier dysfunction and proposes pericytes as a potential therapeutic target. Research shows that the loss of pericytes is closely associated with increased microvascular permeability, abnormal microcirculation, and multi-organ dysfunction in sepsis. Interventions such as activation of the Ang/Tie2 pathway, VEGF inhibition, PDGF-B signaling modulation, and MSC-derived exosomes may effectively restore microvascular stability and alleviate organ damage related to sepsis. The article further explores the integration of cutting-edge technologies such as single-cell genomics and proteomics to precisely identify pericyte function and therapeutic targets, providing new directions and innovative strategies for sepsis treatment.</div></div><div><h3>Background</h3><div>Pericytes are mural cells embedded in the vascular basement membrane and form an integral part of the microvascular structure. Through close interactions with endothelial cells, they participate in vascular remodeling, maintenance of barrier integrity, regulation of capillary blood flow, and protection of the central nervous system. Relevant studies have increasingly emphasized the role of pericytes in sepsis-associated microcirculatory dysfunction, suggesting new directions for therapeutic intervention. This review outlines the biological features of pericytes and their contribution to sepsis-related vascular pathology, with particular attention to mechanisms by which pericytes mediate organ injury. By highlighting key signaling pathways and processes involved in pericyte-driven vascular barrier disruption, we suggest that targeting pericytes may offer a potential strategy for the treatment of sepsis.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104895"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145658873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Invasive coronary physiology assessment and predictors of coronary microvascular dysfunction in patients with diabetes mellitus 糖尿病患者冠状动脉微血管功能障碍的侵袭性冠状动脉生理评估及预测因素。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-01-01 Epub Date: 2025-10-17 DOI: 10.1016/j.mvr.2025.104879

Alice Benedetti , Tijs Bringmans , Maarten Vanhaverbeke , Frédéric Daniel Mathieu , Pieter-Jan Palmers , Patrick Coussement , Kenneth De Wilder , Bert Everaert , Mathieu Coeman , Fabian Demeure , Maarten Kersemans , Peter Kayaert , Jean-François Argacha , Vincent F.M. Segers , Carlo Zivelonghi

Background

Diabetes mellitus (DM) has been associated with coronary microvascular dysfunction (CMD) in previous non-invasive studies. However, invasive studies have shown conflicting results.

Methods

To evaluate the prevalence and predictors of CMD in diabetic patients, invasive coronary physiology data of patients with fractional flow reserve (FFR) > 0.80 on the target vessel were analyzed from the BELmicro registry. Coronary flow reserve (CFR) < 2.5 and index of microcirculatory resistance (IMR) ≥ 25 were considered abnormal.

Results

Out of 402 patients, 72 had DM. Diabetic patients were older [69(61, 75) vs 64(58, 73), p = 0.02] and had higher rates of hypertension (73 % vs 56 %, p = 0.009) and dyslipidemia (89 % vs 64 %, p < 0.001) compared to non-diabetics. No differences were found between diabetic and non-diabetic patients in FFR [0.92(0.89, 0.94) vs 0.91(0.88, 0.94), p = 0.8] and CFR [3.0(2.1, 4.4) vs 2.8(2.0, 4.1), p = 0.4]. IMR was slightly lower in diabetics [16(9, 24) vs 18(12, 27), p = 0.04], but the rate of abnormal IMR was comparable to non-diabetics (23 % vs 31 %, p = 0.2). Prevalence of CMD was similar between diabetics and non-diabetics (46 % vs 48 %, p = 0.8). Rates of CMD were comparable between patients with longstanding DM (≥10 years) and recent diagnosis (52 % vs 35 %, p = 0.2). No association was found between glycated hemoglobin levels and CFR and IMR. Female sex was the only independent predictor of CMD in diabetics (OR: 2.71, 95 % CI: 1.02, 7.50, p = 0.049).

Conclusions

No differences in prevalence of CMD were found between diabetic and non-diabetic patients. Longstanding diabetes, glycemic control and concomitant cardiovascular risk factors were not associated with CMD in diabetic patients.

背景：在以往的非侵入性研究中，糖尿病（DM）与冠状动脉微血管功能障碍（CMD）有关。然而，侵入性研究显示出相互矛盾的结果。方法：为了评估糖尿病患者CMD的患病率及其预测因素，分析BELmicro注册表中靶血管血流储备分数（FFR） > 0.80患者的有创冠状动脉生理学数据。冠状动脉流量储备(CFR) 结果:402名患者,72糖尿病患者老年DM。[69(61、75)和64 (73),p = 0.02],有较高的高血压(73 % vs 56 % p = 0.009)和血脂异常(89 % vs 64 % p 结论:没有发现CMD患病率的差异之间的糖尿病患者和非糖尿病患者。长期糖尿病、血糖控制及伴随的心血管危险因素与糖尿病患者的CMD无关。

{"title":"Invasive coronary physiology assessment and predictors of coronary microvascular dysfunction in patients with diabetes mellitus","authors":"Alice Benedetti , Tijs Bringmans , Maarten Vanhaverbeke , Frédéric Daniel Mathieu , Pieter-Jan Palmers , Patrick Coussement , Kenneth De Wilder , Bert Everaert , Mathieu Coeman , Fabian Demeure , Maarten Kersemans , Peter Kayaert , Jean-François Argacha , Vincent F.M. Segers , Carlo Zivelonghi","doi":"10.1016/j.mvr.2025.104879","DOIUrl":"10.1016/j.mvr.2025.104879","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus (DM) has been associated with coronary microvascular dysfunction (CMD) in previous non-invasive studies. However, invasive studies have shown conflicting results.</div></div><div><h3>Methods</h3><div>To evaluate the prevalence and predictors of CMD in diabetic patients, invasive coronary physiology data of patients with fractional flow reserve (FFR) > 0.80 on the target vessel were analyzed from the BELmicro registry. Coronary flow reserve (CFR) < 2.5 and index of microcirculatory resistance (IMR) ≥ 25 were considered abnormal.</div></div><div><h3>Results</h3><div>Out of 402 patients, 72 had DM. Diabetic patients were older [69(61, 75) vs 64(58, 73), p = 0.02] and had higher rates of hypertension (73 % vs 56 %, p = 0.009) and dyslipidemia (89 % vs 64 %, p < 0.001) compared to non-diabetics. No differences were found between diabetic and non-diabetic patients in FFR [0.92(0.89, 0.94) vs 0.91(0.88, 0.94), p = 0.8] and CFR [3.0(2.1, 4.4) vs 2.8(2.0, 4.1), p = 0.4]. IMR was slightly lower in diabetics [16(9, 24) vs 18(12, 27), p = 0.04], but the rate of abnormal IMR was comparable to non-diabetics (23 % vs 31 %, p = 0.2). Prevalence of CMD was similar between diabetics and non-diabetics (46 % vs 48 %, p = 0.8). Rates of CMD were comparable between patients with longstanding DM (≥10 years) and recent diagnosis (52 % vs 35 %, p = 0.2). No association was found between glycated hemoglobin levels and CFR and IMR. Female sex was the only independent predictor of CMD in diabetics (OR: 2.71, 95 % CI: 1.02, 7.50, p = 0.049).</div></div><div><h3>Conclusions</h3><div>No differences in prevalence of CMD were found between diabetic and non-diabetic patients. Longstanding diabetes, glycemic control and concomitant cardiovascular risk factors were not associated with CMD in diabetic patients.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104879"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nailfold capillaroscopy for early detection of diabetic retinopathy: A non-invasive window into microvascular abnormalities 甲襞毛细血管镜用于糖尿病视网膜病变的早期检测：微血管异常的无创窗口

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-01-01 Epub Date: 2025-10-25 DOI: 10.1016/j.mvr.2025.104881

Fatemeh Azimian Zavareh , Hamid Reza Bashiri , Mohammad Sadegh Dehghani Firouzabadi , Mohammadreza Gholami Banadkoki , Seyed Mohammad Mohammadi , Azam Ghanei

Aims

Diabetic retinopathy (DR) is a leading cause of vision loss in type 2 diabetes mellitus (T2DM), highlighting the need for accessible, non-invasive screening tools. Nail-fold capillaroscopy (NFC) allows in vivo evaluation of microvascular architecture and may provide early markers of DR.

Methods

In this case-control study, 150 T2DM patients (aged 35–75 years) were stratified into DR (n = 75) and non-DR (n = 75) groups. Exclusion criteria included smoking, Raynaud's phenomenon, and ophthalmic comorbidities. NFC images were captured at 200× magnification and analyzed by a blinded rheumatologist. Capillary abnormalities (density, tortuosity, ectasia, crossed-over, bushy, giant capillaries, microhemorrhages, thrombosis) were assessed using validated criteria. Statistical analyses included t-tests, Mann-Whitney U, chi-square, and logistic regression (p < 0.05).

Results

DR patients exhibited significantly higher frequencies of ectatic (p = 0.004), tortuous (p < 0.001), and crossed-over capillaries (p = 0.022) compared to non-DR subjects. Crossed-over vessels were uniquely associated with proliferative DR (p = 0.017), while bushy capillaries were more prevalent in advanced stages (p = 0.021). Sensitivity and specificity for these markers varied, with crossed-over vessels demonstrating 40 % sensitivity and 77.3 % specificity. Capillary tortuosity and ectasia correlated with diabetes duration, whereas crossed-over and bushy vessels were linked to higher BMI.

Conclusions

Nail-fold capillaroscopy reveals distinct microvascular patterns associated with DR and offers a rapid, non-invasive adjunctive screening tool. Crossed-over vessels and tortuosity emerge as practical biomarkers for early risk stratification, particularly in resource-limited settings. Integration with clinical parameters may enhance diagnostic accuracy, supporting timely intervention and prevention of vision loss in high-risk diabetic populations.

糖尿病视网膜病变（DR）是2型糖尿病（T2DM）患者视力丧失的主要原因，这突出了对可获得的非侵入性筛查工具的需求。甲襞毛细血管镜检查（NFC）可以在体内评估微血管结构，并可能提供DR的早期标记。方法在本病例对照研究中，150例T2DM患者（35-75岁）被分为DR （n = 75）组和非DR （n = 75）组。排除标准包括吸烟、雷诺现象和眼部合并症。NFC图像以200倍的放大倍率捕获，并由盲法风湿病学家进行分析。毛细血管异常（密度，扭曲，扩张，交叉，浓密，巨大毛细血管，微出血，血栓形成）使用验证标准进行评估。统计分析包括t检验、Mann-Whitney U检验、卡方检验和logistic回归（p < 0.05）。结果dr患者毛细血管扩张（p = 0.004）、弯曲（p < 0.001）和交叉（p = 0.022）的频率明显高于非dr患者。交叉血管与增殖性DR相关（p = 0.017），而浓密的毛细血管在晚期更为普遍（p = 0.021）。这些标记物的敏感性和特异性各不相同，交叉血管的敏感性为40%，特异性为77.3%。毛细血管扭曲和扩张与糖尿病持续时间相关，而交叉血管和浓密血管与较高的BMI有关。结论甲襞毛细血管镜检查可显示与DR相关的不同微血管模式，是一种快速、无创的辅助筛查工具。交叉血管和扭曲成为早期风险分层的实用生物标志物，特别是在资源有限的情况下。结合临床参数可以提高诊断的准确性，支持及时干预和预防糖尿病高危人群的视力丧失。

{"title":"Nailfold capillaroscopy for early detection of diabetic retinopathy: A non-invasive window into microvascular abnormalities","authors":"Fatemeh Azimian Zavareh , Hamid Reza Bashiri , Mohammad Sadegh Dehghani Firouzabadi , Mohammadreza Gholami Banadkoki , Seyed Mohammad Mohammadi , Azam Ghanei","doi":"10.1016/j.mvr.2025.104881","DOIUrl":"10.1016/j.mvr.2025.104881","url":null,"abstract":"<div><h3>Aims</h3><div>Diabetic retinopathy (DR) is a leading cause of vision loss in type 2 diabetes mellitus (T2DM), highlighting the need for accessible, non-invasive screening tools. Nail-fold capillaroscopy (NFC) allows in vivo evaluation of microvascular architecture and may provide early markers of DR.</div></div><div><h3>Methods</h3><div>In this case-control study, 150 T2DM patients (aged 35–75 years) were stratified into DR (<em>n</em> = 75) and non-DR (n = 75) groups. Exclusion criteria included smoking, Raynaud's phenomenon, and ophthalmic comorbidities. NFC images were captured at 200× magnification and analyzed by a blinded rheumatologist. Capillary abnormalities (density, tortuosity, ectasia, crossed-over, bushy, giant capillaries, microhemorrhages, thrombosis) were assessed using validated criteria. Statistical analyses included <em>t</em>-tests, Mann-Whitney U, chi-square, and logistic regression (<em>p</em> < 0.05).</div></div><div><h3>Results</h3><div>DR patients exhibited significantly higher frequencies of ectatic (<em>p</em> = 0.004), tortuous (<em>p</em> < 0.001), and crossed-over capillaries (<em>p</em> = 0.022) compared to non-DR subjects. Crossed-over vessels were uniquely associated with proliferative DR (<em>p</em> = 0.017), while bushy capillaries were more prevalent in advanced stages (<em>p</em> = 0.021). Sensitivity and specificity for these markers varied, with crossed-over vessels demonstrating 40 % sensitivity and 77.3 % specificity. Capillary tortuosity and ectasia correlated with diabetes duration, whereas crossed-over and bushy vessels were linked to higher BMI.</div></div><div><h3>Conclusions</h3><div>Nail-fold capillaroscopy reveals distinct microvascular patterns associated with DR and offers a rapid, non-invasive adjunctive screening tool. Crossed-over vessels and tortuosity emerge as practical biomarkers for early risk stratification, particularly in resource-limited settings. Integration with clinical parameters may enhance diagnostic accuracy, supporting timely intervention and prevention of vision loss in high-risk diabetic populations.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104881"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic nicotine exposure drives dose-dependent pulmonary hypertension and cardiopulmonary remodeling: Preclinical and clinical validation 慢性尼古丁暴露驱动剂量依赖性肺动脉高压和心肺重塑：临床前和临床验证。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-01-01 Epub Date: 2025-11-14 DOI: 10.1016/j.mvr.2025.104884

Jin Zhou , Xiaomin Hou , Zhifa Zheng , Tingting Quan , Xin Meng , Yi Xu , Liangyuan Zhao , Xiaoxia Ren , Lingbo Yang , Yiwei Shi , Xiaojiang Qin

Pulmonary hypertension (PH) is a severe and life-threatening pulmonary vascular disease. Cigarette smoking is a significant environmental risk factor for PH, and nicotine, a primary toxic component of cigarettes, is closely associated with the development and progression of PH. This study aimed to elucidate the pathological progression of PH induced by chronic nicotine exposure and its dose-dependent effects. We established a murine model of PH by intranasal nicotine instillation in C57BL/6 J mice, coupled with a clinical cohort study of smokers. Using high-resolution echocardiography, right heart catheterization, microvascular tension measurement, and histopathological techniques, we systematically assessed nicotine's dose-dependent effects on pulmonary hemodynamics, vascular function, and cardiac structure and function. Results demonstrated right ventricular systolic pressure (RVSP)—a surrogate for pulmonary arterial (PA) systolic pressure without pulmonary valve stenosis—increased from 18.09 ± 0.28 mmHg (Control) to 31.99 ± 0.21 mmHg (High-dose, P < 0.01). RV hypertrophy and dilation were accompanied by dose-dependent impairment in tricuspid annular plane systolic excursion (TAPSE), declining from 1.83 ± 0.05 mm to 1.15 ± 0.03 mm (P < 0.01). PA abnormalities included shortened acceleration time (PAT), reduced PAT/ejection time ratio, increased PA diameter (PAD), vascular wall thickening, and inflammatory infiltration. Microvascular tension studies confirmed functional impairment. Clinical validation mirrored core findings: in PH patients, smoking index correlated positively with PAD (R² = 0.8553, P < 0.01) and negatively with TAPSE (R² = 0.7523, P < 0.01), strongly corroborating animal data and underscoring nicotine's clinical hazards. Our research demonstrates chronic nicotine exposure induces dose-dependent PH through elevated PA pressure, pulmonary vascular remodeling, and RV dysfunction, providing mechanistic insights for smoking-related PH prevention and treatment.

肺动脉高压（Pulmonary hypertension， PH）是一种严重的危及生命的肺血管疾病。吸烟是PH的重要环境危险因素，尼古丁作为香烟的主要毒性成分，与PH的发生发展密切相关。本研究旨在阐明慢性尼古丁暴露诱导PH的病理进展及其剂量依赖性效应。我们建立了C57BL/6 J小鼠鼻腔内滴入尼古丁的小鼠PH模型，并结合吸烟者的临床队列研究。通过高分辨率超声心动图、右心导管、微血管张力测量和组织病理学技术，我们系统地评估了尼古丁对肺血流动力学、血管功能和心脏结构和功能的剂量依赖性影响。结果证明右心室收缩压(RVSP)——代理为肺动脉(PA)收缩压无肺动脉瓣stenosis-increased 的18.09±0.28  31.99毫米汞柱(控制) ±0.21  毫米汞柱(大剂量P 2 = 0.8553,P 2 = 0.7523,P

{"title":"Chronic nicotine exposure drives dose-dependent pulmonary hypertension and cardiopulmonary remodeling: Preclinical and clinical validation","authors":"Jin Zhou , Xiaomin Hou , Zhifa Zheng , Tingting Quan , Xin Meng , Yi Xu , Liangyuan Zhao , Xiaoxia Ren , Lingbo Yang , Yiwei Shi , Xiaojiang Qin","doi":"10.1016/j.mvr.2025.104884","DOIUrl":"10.1016/j.mvr.2025.104884","url":null,"abstract":"<div><div>Pulmonary hypertension (PH) is a severe and life-threatening pulmonary vascular disease. Cigarette smoking is a significant environmental risk factor for PH, and nicotine, a primary toxic component of cigarettes, is closely associated with the development and progression of PH. This study aimed to elucidate the pathological progression of PH induced by chronic nicotine exposure and its dose-dependent effects. We established a murine model of PH by intranasal nicotine instillation in C57BL/6 J mice, coupled with a clinical cohort study of smokers. Using high-resolution echocardiography, right heart catheterization, microvascular tension measurement, and histopathological techniques, we systematically assessed nicotine's dose-dependent effects on pulmonary hemodynamics, vascular function, and cardiac structure and function. Results demonstrated right ventricular systolic pressure (RVSP)—a surrogate for pulmonary arterial (PA) systolic pressure without pulmonary valve stenosis—increased from 18.09 ± 0.28 mmHg (Control) to 31.99 ± 0.21 mmHg (High-dose, <em>P</em> < 0.01). RV hypertrophy and dilation were accompanied by dose-dependent impairment in tricuspid annular plane systolic excursion (TAPSE), declining from 1.83 ± 0.05 mm to 1.15 ± 0.03 mm (<em>P</em> < 0.01). PA abnormalities included shortened acceleration time (PAT), reduced PAT/ejection time ratio, increased PA diameter (PAD), vascular wall thickening, and inflammatory infiltration. Microvascular tension studies confirmed functional impairment. Clinical validation mirrored core findings: in PH patients, smoking index correlated positively with PAD (R<sup>2</sup> = 0.8553, <em>P</em> < 0.01) and negatively with TAPSE (R<sup>2</sup> = 0.7523, <em>P</em> < 0.01), strongly corroborating animal data and underscoring nicotine's clinical hazards. Our research demonstrates chronic nicotine exposure induces dose-dependent PH through elevated PA pressure, pulmonary vascular remodeling, and RV dysfunction, providing mechanistic insights for smoking-related PH prevention and treatment.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104884"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PAI-1 promotes thromboangiitis obliterans progression through NF-κB-NLRP3 pathway activation via HIF-1α-dependent signaling PAI-1通过hif -1α依赖性信号通路激活NF-κB-NLRP3通路促进血栓闭塞性脉管炎进展。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-01-01 Epub Date: 2025-11-13 DOI: 10.1016/j.mvr.2025.104885

Xiao Xu , Xiaohu Ge , Hongbo Ci , Maitiseyiti Abulaihaiti , JianPing Yang , YangYang Li , Feng Zhu

Background

Thromboangiitis obliterans (TAO, Buerger's disease) is a chronic inflammatory disorder that affects small and medium-sized vessels in the limbs. Although the pathogenesis of TAO remains incompletely understood, elevated levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with cardiovascular diseases. This study investigates the mechanism by which PAI-1 activates the NF-κB/NLRP3 inflammatory pathway in vascular endothelial cells through hypoxia-inducible factor-1α (HIF-1α), contributing to the progression of TAO.

Methods

Proteomic analysis was performed on plasma samples from 5 TAO patients and 5 healthy controls to identify differentially expressed proteins (DEPs). In vitro, human umbilical vein endothelial cells (HUVECs) were subjected to 1 % hypoxia to mimic TAO conditions. Interventions included PAI-1 knockdown using lentiviral vectors and treatment with the HIF-1α agonist dimethyloxalylglycine (DMOG). Cell viability was assessed using the CCK-8 assay, apoptosis was measured by flow cytometry, and inflammatory factor levels were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression was analyzed by Western blotting. In vivo, a TAO rat model was established by sodium laurate injection. The severity of limb ischemia was evaluated using gross lesion grading and infrared thermography, while pathological changes were assessed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining.

Results

Elevated levels of PAI-1, HIF-1α, and key molecules in the NLRP3/NF-κB pathway were observed in both TAO rats and hypoxic HUVECs. PAI-1 knockdown significantly improved limb ischemia and suppressed the NLRP3/NF-κB pathway in TAO rats. Compared with the DMOG intervention group, combined treatment with PAI-1 knockdown and DMOG effectively alleviated ischemic symptoms, increased body weight, and reduced the expression of HIF-1α and inflammatory pathway molecules in TAO rats.

Conclusion

PAI-1 promotes the progression of TAO by activating the NF-κB pathway via HIF-1α. Targeted inhibition of PAI-1 represents a potential therapeutic strategy for TAO.

背景：血栓闭塞性脉管炎（TAO，伯格氏病）是一种影响四肢中小血管的慢性炎症性疾病。虽然TAO的发病机制尚不完全清楚，但纤溶酶原激活物抑制剂-1 （PAI-1）水平升高与心血管疾病有关。本研究探讨PAI-1通过缺氧诱导因子1α (hypoxia-inducible factor-1α, HIF-1α)激活血管内皮细胞NF-κB/NLRP3炎症通路，促进TAO进展的机制。方法：对5例TAO患者和5例健康对照者的血浆样本进行蛋白质组学分析，鉴定差异表达蛋白（DEPs）。体外，将人脐静脉内皮细胞（HUVECs）置于1 %的缺氧条件下模拟TAO条件。干预措施包括使用慢病毒载体敲除PAI-1和使用HIF-1α激动剂二甲基氧基酰甘氨酸（DMOG）治疗。采用CCK-8法评估细胞活力，流式细胞术检测细胞凋亡，酶联免疫吸附试验（ELISA）检测炎症因子水平。Western blotting分析蛋白表达。采用月桂酸钠注射液建立TAO大鼠体内模型。采用肉眼病变分级和红外热像仪评估肢体缺血严重程度，采用苏木精伊红（H&E）染色和马松三色染色评估病理变化。结果：TAO大鼠和缺氧HUVECs中PAI-1、HIF-1α及NLRP3/NF-κB通路关键分子水平均升高。PAI-1敲低可显著改善TAO大鼠肢体缺血，抑制NLRP3/NF-κB通路。与DMOG干预组相比，PAI-1敲低和DMOG联合治疗能有效缓解TAO大鼠的缺血症状，增加体重，降低HIF-1α和炎症途径分子的表达。结论：PAI-1通过HIF-1α激活NF-κB通路，促进TAO的进展。靶向抑制PAI-1是一种潜在的治疗TAO的策略。

{"title":"PAI-1 promotes thromboangiitis obliterans progression through NF-κB-NLRP3 pathway activation via HIF-1α-dependent signaling","authors":"Xiao Xu , Xiaohu Ge , Hongbo Ci , Maitiseyiti Abulaihaiti , JianPing Yang , YangYang Li , Feng Zhu","doi":"10.1016/j.mvr.2025.104885","DOIUrl":"10.1016/j.mvr.2025.104885","url":null,"abstract":"<div><h3>Background</h3><div>Thromboangiitis obliterans (TAO, Buerger's disease) is a chronic inflammatory disorder that affects small and medium-sized vessels in the limbs. Although the pathogenesis of TAO remains incompletely understood, elevated levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with cardiovascular diseases. This study investigates the mechanism by which PAI-1 activates the NF-κB/NLRP3 inflammatory pathway in vascular endothelial cells through hypoxia-inducible factor-1α (HIF-1α), contributing to the progression of TAO.</div></div><div><h3>Methods</h3><div>Proteomic analysis was performed on plasma samples from 5 TAO patients and 5 healthy controls to identify differentially expressed proteins (DEPs). In vitro, human umbilical vein endothelial cells (HUVECs) were subjected to 1 % hypoxia to mimic TAO conditions. Interventions included PAI-1 knockdown using lentiviral vectors and treatment with the HIF-1α agonist dimethyloxalylglycine (DMOG). Cell viability was assessed using the CCK-8 assay, apoptosis was measured by flow cytometry, and inflammatory factor levels were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression was analyzed by Western blotting. In vivo, a TAO rat model was established by sodium laurate injection. The severity of limb ischemia was evaluated using gross lesion grading and infrared thermography, while pathological changes were assessed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining.</div></div><div><h3>Results</h3><div>Elevated levels of PAI-1, HIF-1α, and key molecules in the NLRP3/NF-κB pathway were observed in both TAO rats and hypoxic HUVECs. PAI-1 knockdown significantly improved limb ischemia and suppressed the NLRP3/NF-κB pathway in TAO rats. Compared with the DMOG intervention group, combined treatment with PAI-1 knockdown and DMOG effectively alleviated ischemic symptoms, increased body weight, and reduced the expression of HIF-1α and inflammatory pathway molecules in TAO rats.</div></div><div><h3>Conclusion</h3><div>PAI-1 promotes the progression of TAO by activating the NF-κB pathway via HIF-1α. Targeted inhibition of PAI-1 represents a potential therapeutic strategy for TAO.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104885"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between posterior vitreous detachment stage and quantitative neovascularization morphology in proliferative diabetic retinopathy using wide-field swept-source optical coherence tomography angiography 增生性糖尿病视网膜病变后玻璃体脱离阶段与定量新生血管形态的关系。

IF 2.7 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research

Pub Date : 2026-01-01 Epub Date: 2025-09-19 DOI: 10.1016/j.mvr.2025.104875

Zikang Xu , Ruoyu Chen , Jing Li , Danling Huang , Taozheng Li , Huilin Liang , Zhicong Xu , Jiayi Huang , Mi Gui , I.M. Hojas , Xuenan Zhuang , Liang Zhang

Purpose

To investigate the association between posterior vitreous detachment (PVD) and the progression of proliferative diabetic retinopathy (PDR) by analyzing the morphological evolution of neovascularization (NV) across PVD stages using swept-source optical coherence tomography angiography (SS-OCTA).

Methods

This retrospective study assessed PVD stages via SS-OCT. Quantitative analysis of SS-OCTA images was performed with ImageJ and AngioTool to extract NV morphological features including perimeter, MaxFeret, MiniFeret, Feret ratio (FR), maximum vessel caliber, vessel dispersion, fractal dimension index (FDI), vessel area (VA), vessel density, total vessel length (TVL), average vessel length (AVL), total number of junctions (TNJ), junction density (JD), total number of endpoints, endpoint density (ED), and mean lacunarity (MEL) to assess NV size, activity, and complexity. Analysis of NV morphology and PVD association via Generalized Linear Mixed Model.

Results

Significant differences (P < 0.05) in multiple NV parameters were observed across PVD stages in the 74 included eyes. At stage 4, most parameters reached their minima, except for JD and ED, which peaked. Trend analysis revealed inverted U-shaped trajectories for size (perimeter, MaxFeret, MiniFeret, VA), activity (TNJ, TVL, AVL), and complexity (FDI) parameters with PVD progression. In contrast, JD and ED followed U-shaped trends. All inflection points clustered between stages 1 and 2.

Conclusions

NV morphology in PDR evolves systematically from a highly intricate and extensive structure in early PVD (Stage 1 or 2) to a simplified and localized architecture in stage 4. Concomitant alterations in NV activity and complexity likely occur, providing morphological insights into PVD's role in PDR.

目的：通过扫描源光学相干断层扫描血管造影（SS-OCTA）分析PVD分期新生血管（NV）的形态学演变，探讨玻璃体后脱离（PVD）与增生性糖尿病视网膜病变（PDR）进展之间的关系。方法：本回顾性研究通过SS-OCT评估PVD分期。使用ImageJ和AngioTool对SS-OCTA图像进行定量分析，提取NV形态学特征，包括周长、MaxFeret、MiniFeret、Feret比率（FR）、最大血管直径、血管离散度、分形维指数（FDI）、血管面积（VA）、血管密度、血管总长度（TVL）、血管平均长度（AVL）、总结数（TNJ）、结密度（JD）、总端点数、端点密度（ED）和平均间隙度（MEL），以评估NV大小。活动和复杂性。广义线性混合模型分析NV形态与PVD关联。结果：显著差异(P 结论：PDR的NV形态系统地从早期PVD（1或2期）的高度复杂和广泛的结构演变为4期的简化和局部结构。同时可能发生NV活性和复杂性的改变，这为PVD在PDR中的作用提供了形态学上的见解。

{"title":"Association between posterior vitreous detachment stage and quantitative neovascularization morphology in proliferative diabetic retinopathy using wide-field swept-source optical coherence tomography angiography","authors":"Zikang Xu , Ruoyu Chen , Jing Li , Danling Huang , Taozheng Li , Huilin Liang , Zhicong Xu , Jiayi Huang , Mi Gui , I.M. Hojas , Xuenan Zhuang , Liang Zhang","doi":"10.1016/j.mvr.2025.104875","DOIUrl":"10.1016/j.mvr.2025.104875","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the association between posterior vitreous detachment (PVD) and the progression of proliferative diabetic retinopathy (PDR) by analyzing the morphological evolution of neovascularization (NV) across PVD stages using swept-source optical coherence tomography angiography (SS-OCTA).</div></div><div><h3>Methods</h3><div>This retrospective study assessed PVD stages via SS-OCT. Quantitative analysis of SS-OCTA images was performed with ImageJ and AngioTool to extract NV morphological features including perimeter, MaxFeret, MiniFeret, Feret ratio (FR), maximum vessel caliber, vessel dispersion, fractal dimension index (FDI), vessel area (VA), vessel density, total vessel length (TVL), average vessel length (AVL), total number of junctions (TNJ), junction density (JD), total number of endpoints, endpoint density (ED), and mean lacunarity (MEL) to assess NV size, activity, and complexity. Analysis of NV morphology and PVD association via Generalized Linear Mixed Model.</div></div><div><h3>Results</h3><div>Significant differences (<em>P</em> < 0.05) in multiple NV parameters were observed across PVD stages in the 74 included eyes. At stage 4, most parameters reached their minima, except for JD and ED, which peaked. Trend analysis revealed inverted U-shaped trajectories for size (perimeter, MaxFeret, MiniFeret, VA), activity (TNJ, TVL, AVL), and complexity (FDI) parameters with PVD progression. In contrast, JD and ED followed U-shaped trends. All inflection points clustered between stages 1 and 2.</div></div><div><h3>Conclusions</h3><div>NV morphology in PDR evolves systematically from a highly intricate and extensive structure in early PVD (Stage 1 or 2) to a simplified and localized architecture in stage 4. Concomitant alterations in NV activity and complexity likely occur, providing morphological insights into PVD's role in PDR.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104875"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0