The endothelial glycocalyx (eGCX), a delicate carbohydrate-rich layer coating the vascular endothelium, critically regulates vascular homeostasis, controlling permeability, thrombosis, and inflammation. Despite its fundamental importance, assessing the morphology of the eGCX remains technically challenging because of its fragile structure, which collapses during conventional fixation. Existing visualization methods require complex preparation, expensive equipment, and fresh tissues, severely limiting accessibility and clinical applicability. Here, we present a practical approach for visualizing and semi-quantitatively phenotyping the eGCX using formalin-fixed, paraffin-embedded (FFPE) tissue sections prepared via specialized Alcian blue fixation, followed by strategic integration of silver enhancement staining and low-vacuum scanning electron microscopy. The proposed method enabled robust visualization of eGCX across multiple vascular beds, including brain parenchymal vessels, choroid plexus fenestrated capillaries, and retinal vasculature, along with a thickness-based index suitable for between-condition comparisons among FFPE sections. The technique demonstrated high sensitivity in detecting pathological alterations, evidenced by near-complete eGCX loss in retinal vein occlusion models with significant reductions in thickness and lectin fluorescence intensity. Finally, the workflow was successfully applied to human colorectal surgical specimens processed via immediate Alcian blue immersion fixation, enabling visualization of vascular eGCX in FFPE clinical sections. Overall, these findings support an accessible FFPE-compatible approach for wide-field eGCX imaging and pathology-oriented phenotyping.
{"title":"Practical method for endothelial glycocalyx imaging in formalin-fixed, paraffin-embedded tissues in vascular pathology","authors":"Kosuke Mori , Hiroyuki Tomita , Masashi Kuno , Tomohiro Iida , Yoshihiko Yamakita , Chihiro Takada , Aika Kuriyama , Shinsuke Nakamura , Masamitsu Shimazawa , Toshiaki Hirose , Mayu Sakakibara , Hidetaka Suga , Shigeyuki Sugie , Hideshi Okada , Akira Hara","doi":"10.1016/j.mvr.2026.104913","DOIUrl":"10.1016/j.mvr.2026.104913","url":null,"abstract":"<div><div>The endothelial glycocalyx (eGCX), a delicate carbohydrate-rich layer coating the vascular endothelium, critically regulates vascular homeostasis, controlling permeability, thrombosis, and inflammation. Despite its fundamental importance, assessing the morphology of the eGCX remains technically challenging because of its fragile structure, which collapses during conventional fixation. Existing visualization methods require complex preparation, expensive equipment, and fresh tissues, severely limiting accessibility and clinical applicability. Here, we present a practical approach for visualizing and semi-quantitatively phenotyping the eGCX using formalin-fixed, paraffin-embedded (FFPE) tissue sections prepared via specialized Alcian blue fixation, followed by strategic integration of silver enhancement staining and low-vacuum scanning electron microscopy. The proposed method enabled robust visualization of eGCX across multiple vascular beds, including brain parenchymal vessels, choroid plexus fenestrated capillaries, and retinal vasculature, along with a thickness-based index suitable for between-condition comparisons among FFPE sections. The technique demonstrated high sensitivity in detecting pathological alterations, evidenced by near-complete eGCX loss in retinal vein occlusion models with significant reductions in thickness and lectin fluorescence intensity. Finally, the workflow was successfully applied to human colorectal surgical specimens processed via immediate Alcian blue immersion fixation, enabling visualization of vascular eGCX in FFPE clinical sections. Overall, these findings support an accessible FFPE-compatible approach for wide-field eGCX imaging and pathology-oriented phenotyping.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"165 ","pages":"Article 104913"},"PeriodicalIF":2.7,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046391","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":"Blood viscosity – The unifying cardiovascular disease risk biomarker","authors":"Erik Finlayson","doi":"10.1016/j.mvr.2026.104904","DOIUrl":"10.1016/j.mvr.2026.104904","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Blood viscosity is associated with all known cardiovascular risk factors.</div></span></li><li><span>•</span><span><div>The treatment of all known cardiovascular risk factors also decreases blood viscosity.</div></span></li><li><span>•</span><span><div>The measurement of blood viscosity may help to guide the treatment of cardiovascular disease risk.</div></span></li></ul></div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"164 ","pages":"Article 104904"},"PeriodicalIF":2.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998529","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":"Distribution and microstructure of the endothelial glycocalyx in the blood-brain barrier","authors":"Kyunghwun Chung , Jae Gyeong Kim , Chungyoul Choe , Seongtae Jeong","doi":"10.1016/j.mvr.2026.104903","DOIUrl":"10.1016/j.mvr.2026.104903","url":null,"abstract":"","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"165 ","pages":"Article 104903"},"PeriodicalIF":2.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989831","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}
Pub Date : 2026-01-06DOI: 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.
{"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":"2026-01-06","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}
Pub Date : 2025-12-22DOI: 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.
{"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":"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}
To investigate gender differences in retinal and choroidal thickness and vascular density (VD) among myopic children using swept-source OCT angiography (SS-OCTA).
Methods
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.
Results
Females showed significantly lower foveal and parafoveal superficial vascular complex (SVC) and macular choriocapillaris (CC) VD (all P < 0.05). Axial length (AL) correlated positively with foveal and parafoveal thickness and VD, and negatively in the perifovea (all P < 0.05).It also positively correlated with RNFL and GCC thickness, SVC, and RPC VD in temporal optic-disc sectors (r = 0.11 to 0.19, P < 0.01), and negatively in nasal sectors (r = −0.11 to −0.23, P < 0.01). In males, correlations between AL and foveal SVC VD (Z = −2.53, P < 0.05), AL and parafoveal deep vascular complex VD (Z = −2.34, P < 0.05), and SE and perifoveal CC VD (Z = −2.82, P < 0.01) were significantly stronger.
Conclusions
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.
{"title":"Comparative analysis of retinal and choroidal microvascular characteristics by gender in myopic children: A SS-OCTA study","authors":"Ting Guo , Mingli He , Fangyuan Zhou , Ruoyu Zhang , Yishuang Xu , Zhen Chen , 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> < 0.05). Axial length (AL) correlated positively with foveal and parafoveal thickness and VD, and negatively in the perifovea (all <em>P</em> < 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> < 0.01), and negatively in nasal sectors (<em>r</em> = −0.11 to −0.23, P < 0.01). In males, correlations between AL and foveal SVC VD (Z = −2.53, P < 0.05), AL and parafoveal deep vascular complex VD (Z = −2.34, P < 0.05), and SE and perifoveal CC VD (Z = −2.82, P < 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}
Pub Date : 2025-12-13DOI: 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.
{"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":"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}
Pub Date : 2025-12-07DOI: 10.1016/j.mvr.2025.104896
M.S. Josef
Background
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.
Methods
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.
Results
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.
Conclusions
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.
背景：血管直径被认为是对可溶性鸟苷酸环化酶（sGC）调节剂的反应性的决定因素，但现有的证据在物种和实验环境中仍然存在差异。了解这些关系对于改善sGC刺激剂和激活剂的翻译解释和治疗使用是重要的。方法：根据PRISMA原则进行系统综述，确定体外、体内和临床研究，检查血管或信号对sGC刺激剂或激活剂在规定直径的血管中的反应。提取有关血管类型、大小、种类、疾病模型、化合物类别和测量结果（如血管松弛或环鸟苷单磷酸（cGMP）产生）的数据。采用sycle、Cochrane RoB 2.0和ROBINS-I工具评估方法学质量和偏倚风险。在主要检索后发现的其他相关研究被总结为支持证据。结果：53项研究符合纳入标准（38项临床前研究，15项临床研究）。一般来说，较小的血管对sGC激活剂表现出更强的舒张和更高的cGMP反应，而sGC刺激剂的证据则更加不均匀，并且不太一致地依赖于直径。这种关系的大小随物种、血管床、氧化或病理条件而变化。人体组织研究通常缺乏诸如缺血时间或供体特征等分析前因素的信息。在整个研究设计中，偏倚风险评估显示主要是中度或高风险，主要是由于方法学报告不完整和混淆控制有限。结论：目前的证据支持血管对sGC调节剂反应的大小依赖模式，但推断强度受到不同方法和不一致报道的限制。未来的工作应该实施标准化的血管分类、严格的生物标本处理和透明的方法学文件，以阐明血管直径在sgc治疗中的临床意义。
{"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}
Pub Date : 2025-12-06DOI: 10.1016/j.mvr.2025.104897
Laura Palacios-Abril , Aroa Tardáguila-García , Francisco Javier Álvaro-Afonso , Sol Tejeda-Ramírez , Mateo López-Moral , José Luis Lázaro-Martínez
Introduction
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.
Material and methods
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.
Results
Overall, microvascular parameters, particularly skin perfusion pressure, increased significantly by 15 % (p = 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.
Conclusion
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.
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