Microvascular research最新文献

{"title":"Quantitative evaluation of retinal vascular morphology based on the human visual bionic mechanism for the evaluation of diabetic retinopathy onset","authors":"Yi Xu ,&nbsp;Yuting Wu ,&nbsp;Saiguang Ling ,&nbsp;Zhou Dong ,&nbsp;Xin Ke ,&nbsp;Lina Lu ,&nbsp;Zheng Ye ,&nbsp;Jianling Song ,&nbsp;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> &gt; 0.05). However, DR onset was significantly correlated with retinal arteriolar caliber, fractal dimensions, and retinal venular tortuosity (<em>P</em> &lt; 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":"2026-01-06","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}

{"title":"Erythrocyte rheology under anesthesia: Insights from glycated and non-glycated red blood cells","authors":"Marcus V. Batista da Silva ,&nbsp;Horacio V. Castellini ,&nbsp;Nicolás A. Alet ,&nbsp;Bibiana D. Riquelme ,&nbsp;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":"2025-12-22","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}

{"title":"Comparative analysis of retinal and choroidal microvascular characteristics by gender in myopic children: A SS-OCTA study","authors":"Ting Guo ,&nbsp;Mingli He ,&nbsp;Fangyuan Zhou ,&nbsp;Ruoyu Zhang ,&nbsp;Yishuang Xu ,&nbsp;Zhen Chen ,&nbsp;Dihao Hua","doi":"10.1016/j.mvr.2025.104899","DOIUrl":"10.1016/j.mvr.2025.104899","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate gender differences in retinal and choroidal thickness and vascular density (VD) among myopic children using swept-source OCT angiography (SS-OCTA).</div></div><div><h3>Methods</h3><div>This cross-sectional study included 673 Chinese myopic children (8–16 years; 305 males, 368 females). Macular and optic disc regions were imaged. Parameters were compared using ANCOVA adjusted for age and refractive error, with supplementary partial correlation analyses.</div></div><div><h3>Results</h3><div>Females showed significantly lower foveal and parafoveal superficial vascular complex (SVC) and macular choriocapillaris (CC) VD (all <em>P</em> &lt; 0.05). Axial length (AL) correlated positively with foveal and parafoveal thickness and VD, and negatively in the perifovea (all <em>P</em> &lt; 0.05).It also positively correlated with RNFL and GCC thickness, SVC, and RPC VD in temporal optic-disc sectors (<em>r</em> = 0.11 to 0.19, <em>P</em> &lt; 0.01), and negatively in nasal sectors (<em>r</em> = −0.11 to −0.23, P &lt; 0.01). In males, correlations between AL and foveal SVC VD (Z = −2.53, P &lt; 0.05), AL and parafoveal deep vascular complex VD (Z = −2.34, P &lt; 0.05), and SE and perifoveal CC VD (Z = −2.82, P &lt; 0.01) were significantly stronger.</div></div><div><h3>Conclusions</h3><div>Females exhibited reduced SVC and CC VD. Both genders showed significant associations between refractive parameters and vascular parameters, with partially stronger correlations observed in males. These gender differences in ocular blood flow suggest that gender may influence vascular alterations associated with myopia, warranting further research. Recognition of gender-based differences in ocular vasculature and structure may inform individualized myopia-control strategies and improve treatment efficacy across genders.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104899"},"PeriodicalIF":2.7,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810387","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}

{"title":"Impact of the menstrual cycle phase on microvascular function at high altitude","authors":"Guia Tagliapietra ,&nbsp;Giorgio Manferdelli ,&nbsp;Tom Citherlet ,&nbsp;Antoine Raberin ,&nbsp;Benjamin J. Narang ,&nbsp;Tadej Debevec ,&nbsp;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 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 %; <em>p</em> = 0.559), desaturation rate (−0.086 ± 0.061 vs. −0.080 ± 0.039 %·s⁻¹; <em>p</em> = 0.920), normalized reperfusion slope (0.013 ± 0.010 vs. 0.014 ± 0.005 %·s⁻¹; <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":"2025-12-13","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}

{"title":"Vascular diameter and responsiveness to soluble guanylate cyclase modulators: A systematic review of preclinical and clinical evidence","authors":"M.S. Josef","doi":"10.1016/j.mvr.2025.104896","DOIUrl":"10.1016/j.mvr.2025.104896","url":null,"abstract":"<div><h3>Background</h3><div>Vessel diameter has been proposed as a determinant of responsiveness to soluble guanylate cyclase (sGC) modulators, but available evidence remains heterogeneous across species and experimental settings. Understanding these relationships is important for improving translational interpretation and therapeutic use of sGC stimulators and activators.</div></div><div><h3>Methods</h3><div>A systematic review was performed according to PRISMA principles, identifying in vitro, in vivo, and clinical studies that examined vascular or signaling responses to sGC stimulators or activators in vessels of defined diameter. Data were extracted on vessel type, size, species, disease model, compound class, and measured outcomes such as vasorelaxation or cyclic guanosine monophosphate (cGMP) production. Methodological quality and risk of bias were assessed using SYRCLE, Cochrane RoB 2.0, and ROBINS-I tools. Additional relevant studies identified after the main search were summarized as supporting evidence.</div></div><div><h3>Results</h3><div>Fifty-three studies met inclusion criteria (thirty-eight preclinical, fifteen clinical). In general, smaller vessels showed stronger relaxation and higher cGMP responses to sGC activators, while the evidence for sGC stimulators was more heterogeneous and less consistently diameter-dependent. The magnitude of this relationship varied with species, vascular bed, and oxidative or pathological conditions. Human tissue studies often lacked information on pre-analytical factors such as ischemia time or donor characteristics. Across study designs, risk-of-bias assessment indicated predominantly moderate or high risk, largely due to incomplete methodological reporting and limited control for confounding.</div></div><div><h3>Conclusions</h3><div>Current evidence supports a size-dependent pattern of vascular responsiveness to sGC modulators, but inference strength is constrained by heterogeneous methodologies and inconsistent reporting. Future work should implement standardized vessel classification, rigorous biospecimen handling, and transparent methodological documentation to clarify the clinical significance of vessel diameter in sGC-based therapy.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104896"},"PeriodicalIF":2.7,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715045","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}

{"title":"Fifteen-minute walk improves microcirculation in people with diabetes mellitus","authors":"Laura Palacios-Abril ,&nbsp;Aroa Tardáguila-García ,&nbsp;Francisco Javier Álvaro-Afonso ,&nbsp;Sol Tejeda-Ramírez ,&nbsp;Mateo López-Moral ,&nbsp;José Luis Lázaro-Martínez","doi":"10.1016/j.mvr.2025.104897","DOIUrl":"10.1016/j.mvr.2025.104897","url":null,"abstract":"<div><h3>Introduction</h3><div>Skin perfusion is a key marker for detecting microcirculatory disorders in the lower extremity and predicting complications in patients with diabetes mellitus. This study aimed to evaluate microcirculation before and after an external stimulus—characterised by tissue hypoxia, increased temperature, and pressure—to assess its effect on tissue perfusion.</div></div><div><h3>Material and methods</h3><div>A pre–post analytical study was conducted in 30 participants. Baseline measurements included skin perfusion pressure, digital, ankle, and toe pressures, and transcutaneous oxygen pressure, obtained using a combined sphygmomanometry and laser Doppler flowmetry system. Sensors were placed on the dorsum of the foot, pads of both great toes, and the third finger of the hand, with pneumatic cuffs on the upper arm, ankles, and toes. Ankle–brachial and toe–brachial indices were calculated. Participants then completed a supervised 15-minute treadmill walk at 2.5 km/h, after which all measurements were repeated. Notable changes in participants with compromised vascular status prompted an exploratory subgroup analysis. Risk of ulceration was defined according to the International Working Group on the Diabetic Foot classification, based on loss of protective sensation, peripheral arterial disease, foot deformity, and any prior ulceration or amputation. Ischaemia was classified using the Wound, Ischaemia and Foot Infection system, which grades severity according to ankle–brachial index, toe pressure, and transcutaneous oxygen pressure. Stratification using these internationally recognised classifications provided a standardised framework to interpret the responses in a clinically meaningful context. Effects across subgroups were analysed using one-factor analysis of variance, evaluating both absolute and relative changes to account for baseline heterogeneity.</div></div><div><h3>Results</h3><div>Overall, microvascular parameters, particularly skin perfusion pressure, increased significantly by 15 % (<em>p</em> = 0.035, d = −0.412) after the intervention, whereas macrovascular parameters remained unchanged. Subgroup analyses revealed no statistically significant differences, but potentially relevant increases of up to 33 % in tissue perfusion were observed, especially in participants with compromised vascular status.</div></div><div><h3>Conclusion</h3><div>This simple, non-pharmacological stimulus may effectively enhance tissue perfusion in patients with diabetes mellitus, particularly in those at high risk of ulceration or with moderate to severe ischaemia, offering clinically feasible intervention.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104897"},"PeriodicalIF":2.7,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708563","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}

{"title":"Pericytes at the crossroads of sepsis: Mechanisms and therapeutic opportunities in vascular barrier dysfunction","authors":"Changhong Miao ,&nbsp;Lu Xiao ,&nbsp;Xinyi Xu ,&nbsp;Jingchao Miao ,&nbsp;Jiajin Liu ,&nbsp;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":"2025-12-03","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}

{"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 ,&nbsp;K. Sreekanth ,&nbsp;G. Aparna ,&nbsp;C. Chandana ,&nbsp;N. Radhakrishnan ,&nbsp;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":"2025-11-26","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}

{"title":"Chronic nicotine exposure drives dose-dependent pulmonary hypertension and cardiopulmonary remodeling: Preclinical and clinical validation","authors":"Jin Zhou ,&nbsp;Xiaomin Hou ,&nbsp;Zhifa Zheng ,&nbsp;Tingting Quan ,&nbsp;Xin Meng ,&nbsp;Yi Xu ,&nbsp;Liangyuan Zhao ,&nbsp;Xiaoxia Ren ,&nbsp;Lingbo Yang ,&nbsp;Yiwei Shi ,&nbsp;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> &lt; 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> &lt; 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, <em>P</em> &lt; 0.01) and negatively with TAPSE (R² = 0.7523, <em>P</em> &lt; 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":"2025-11-14","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}

{"title":"PAI-1 promotes thromboangiitis obliterans progression through NF-κB-NLRP3 pathway activation via HIF-1α-dependent signaling","authors":"Xiao Xu ,&nbsp;Xiaohu Ge ,&nbsp;Hongbo Ci ,&nbsp;Maitiseyiti Abulaihaiti ,&nbsp;JianPing Yang ,&nbsp;YangYang Li ,&nbsp;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&amp;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":"2025-11-13","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}