Microvascular research最新文献

{"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":"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}

{"title":"Invasive coronary physiology assessment and predictors of coronary microvascular dysfunction in patients with diabetes mellitus","authors":"Alice Benedetti ,&nbsp;Tijs Bringmans ,&nbsp;Maarten Vanhaverbeke ,&nbsp;Frédéric Daniel Mathieu ,&nbsp;Pieter-Jan Palmers ,&nbsp;Patrick Coussement ,&nbsp;Kenneth De Wilder ,&nbsp;Bert Everaert ,&nbsp;Mathieu Coeman ,&nbsp;Fabian Demeure ,&nbsp;Maarten Kersemans ,&nbsp;Peter Kayaert ,&nbsp;Jean-François Argacha ,&nbsp;Vincent F.M. Segers ,&nbsp;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) &gt; 0.80 on the target vessel were analyzed from the BELmicro registry. Coronary flow reserve (CFR) &lt; 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 &lt; 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}

{"title":"Nailfold capillaroscopy for early detection of diabetic retinopathy: A non-invasive window into microvascular abnormalities","authors":"Fatemeh Azimian Zavareh ,&nbsp;Hamid Reza Bashiri ,&nbsp;Mohammad Sadegh Dehghani Firouzabadi ,&nbsp;Mohammadreza Gholami Banadkoki ,&nbsp;Seyed Mohammad Mohammadi ,&nbsp;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> &lt; 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> &lt; 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}

{"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":"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}

{"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 ,&nbsp;Ruoyu Chen ,&nbsp;Jing Li ,&nbsp;Danling Huang ,&nbsp;Taozheng Li ,&nbsp;Huilin Liang ,&nbsp;Zhicong Xu ,&nbsp;Jiayi Huang ,&nbsp;Mi Gui ,&nbsp;I.M. Hojas ,&nbsp;Xuenan Zhuang ,&nbsp;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> &lt; 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}

{"title":"Sex differences in near-infrared spectroscopy reactive hyperemia: Influence of adipose tissue and desaturation rate","authors":"Matthew A. Chatlaong ,&nbsp;Hannah C. Dowell ,&nbsp;Orlandria J. Smith ,&nbsp;Matthew B. Jessee","doi":"10.1016/j.mvr.2025.104865","DOIUrl":"10.1016/j.mvr.2025.104865","url":null,"abstract":"<div><div>Sex differences in near-infrared spectroscopy (NIRS) reactive hyperemia outcomes have been previously reported, with females generally having a lower reperfusion slope. Sex differences have also been reported for adipose tissue thickness (ATT), which affects the NIRS signal, and desaturation during occlusion, which may act on reperfusion slopes. We aimed to compare statistically adjusted and unadjusted sex differences in reperfusion slope during reactive hyperemia.</div></div><div><h3>Methods</h3><div>23 female and 22 male participants completed forearm and thigh vascular occlusion tests. ATT was measured via ultrasound. Reperfusion slopes (StO₂%/s) were compared between sexes using linear models with and without desaturation slope (StO₂%/s) and ATT as covariates. Results are mean or mean difference [95 % CI].</div></div><div><h3>Results</h3><div>In both limbs, females had greater ATT (<em>p</em> &lt; 0.001). Desaturation rate was lower in females for the leg (−0.02 [−0.03, −0.01]), but not the arm (0.00 [−0.01, 0.02]). Unadjusted, males had greater reperfusion slope in the leg (females = 0.91 [0.70, 1.11], males = 1.59 [1.33, 1.85], <em>p</em> &lt; 0.001) but not the arm (females = 1.60 [1.36, 1.84], males = 1.57 [1.29, 1.86], <em>p</em> = 0.874). Sex differences were not observed in adjusted models (both <em>p</em> ≥ 0.631). ATT and desaturation slope explained unique variance in the leg (both <em>p</em> ≤ 0.001), but only desaturation slope did in the arm (<em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Sex differences may have been related to differing ATT and desaturation rates. Researchers may consider adjusting for ATT and/or desaturation rate when estimating sex differences with NIRS reactive hyperemia.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104865"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030165","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":"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}

{"title":"Clinical profile and long-term outcomes of chest pain patients with coronary microvascular dysfunction from the emergency department – results from the Yale-CMD registry","authors":"Basmah Safdar ,&nbsp;Bin Zhou ,&nbsp;Fangyong Li ,&nbsp;Paolo G. Camici ,&nbsp;James Dziura ,&nbsp;Ania M. Jastreboff ,&nbsp;Alexandra Lansky ,&nbsp;Samit M. Shah ,&nbsp;Albert Sinusas ,&nbsp;Erica Spatz ,&nbsp;Gail D'Onofrio","doi":"10.1016/j.mvr.2025.104878","DOIUrl":"10.1016/j.mvr.2025.104878","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the long-term prognosis of coronary microvascular dysfunction (CMD) in emergency department (ED) patients with chest pain for major adverse cardiac events (MACE) due to all-cause mortality, myocardial infarction (MI), heart failure (HF), or stroke.</div></div><div><h3>Methods</h3><div>A prospective cohort of ED patients evaluated by hybrid cardiac positron emission tomography with attenuation computed tomography within 24 h of arrival. Patients were classified as: (1) Controls – coronary flow reserve (CFR) ≥2 without perfusion defect or coronary calcification; (2) CMD: CFR &lt;2 without defect or calcification; or (3) CAD/CALC – established or new coronary artery disease (CAD) or calcification (CALC). We conducted annual follow-ups for MACE and all-cause healthcare utilization (hospitalizations and ED visits). We adjusted incidence rates (aIR) and hazard ratio (aHR) for demographics, comorbidities, and medications.</div></div><div><h3>Results</h3><div>Between 2014 and 2020, 189 patients were enrolled: 95 (50 %) Controls, 34 (18 %) with CMD, and 60 (32 %) with CAD/CALC. Median follow-up time was 50 months (38–92), and a total of 187 unique MACE were recorded in 44 patients. CMD patients had 4× higher MACE risk than controls (aIR 3.8; 95 % CI: 2.1–6.6). CAD/CALC patients had similarly higher risk than controls (aIR: 4.5; 95 % CI: 2.6–7.8). CMD patients had 4× higher risk for time to first MACE than controls (aHR: 3.6; 95 % CI: 1.2–10.7) and higher healthcare utilization per 100 person-months (aIR: 124; 95 % CI: 119–130). Using Seattle Angina Questionnaire, CMD patients showed worse angina frequency than controls (difference: -16.4, 95 % CI: −29.5 to −3.4).</div></div><div><h3>Conclusions</h3><div>Patients with contemporary phenotypes of ischemia (CMD and CAD/CALC) had higher adverse events than controls, positing ED encounters as an opportunity for early identification and treatment.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104878"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329555","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":"DOT1L-mediated H3K79me1 transcriptional activation of Acp5 aggravates inflammatory responses following diabetic vascular injury","authors":"Jing Zhang ,&nbsp;Zishu Yang ,&nbsp;Li Liu ,&nbsp;Di Wu ,&nbsp;Chen Cheng ,&nbsp;Peng Zhu ,&nbsp;Wei Wang ,&nbsp;Wenqiang Li ,&nbsp;Hua Deng ,&nbsp;Yudiyang Ma ,&nbsp;Cuiyuan Huang ,&nbsp;Jian Yang","doi":"10.1016/j.mvr.2025.104882","DOIUrl":"10.1016/j.mvr.2025.104882","url":null,"abstract":"<div><h3>Background</h3><div>Hyperinsulinemia-induced inflammatory responses are a key pathological basis for diabetic proliferative vascular lesions. However, DOT1L impact on vascular repair following diabetic injury and the underlying mechanism remain unclear.</div></div><div><h3>Methods</h3><div>Recombinant lentiviral vectors were constructed to target the upregulation or downregulation of DOT1L expression. Carotid artery balloon injury (BI) model was established in diabetic rats. In vitro experiments, an insulin (INS)-stimulated vascular smooth muscle cell (VSMC) model was used. Inflammatory factor levels, vascular intimal hyperplasia and hemodynamics, H3K79me enrichment in promoter regions were detected. ChIP-Seq was used to evaluate the distribution of proteins and genes, and the levels of proteins implicated in related pathways were analyzed.</div></div><div><h3>Results</h3><div>We found that both in diabetic rat carotid artery tissues 28 days post-BI and in VSMCs after 12 h of insulin stimulation, DOT1L, H3K79me1, IL-6 and TNF-α levels were markedly increased. Overexpression of DOT1L enhanced the expression and release of IL-6 and TNF-α in insulin-induced VSMCs, increased the enrichment of H3K79me1 at the Acp5 gene promoter by 3.92-fold, promoted ACP5 expression, inhibited β-catenin phosphorylation, and upregulated NLRP3 levels. Conversely, downregulation of DOT1L had the opposite effects. In arteries overexpressing DOT1L, inflammatory factor expression and release were markedly enhanced, accompanied by triggering of the ACP5/β-catenin/NLRP3 signaling pathway, roughened intimal surfaces, reduced lumen diameters, decreased residual blood flow area, and increased diameter stenosis rate; greater intimal thickness, and a higher intima/media ratio. In contrast, downregulation of DOT1L exhibited opposite effects.</div></div><div><h3>Conclusion</h3><div>DOT1L aggravates the inflammatory response following diabetic vascular injury by transcriptionally activating Acp5 through H3K79me1, inhibiting β-catenin phosphorylation and inactivation, and upregulating NLRP3 expression.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104882"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445309","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":"Involvement of monocarboxylate transporter 7 in taurine efflux transport from rat retinal pericytes and capillary endothelial cells","authors":"Yuma Tega ,&nbsp;Fuki Kusakabe ,&nbsp;Shin-ichi Akanuma ,&nbsp;Ken-ichi Hosoya","doi":"10.1016/j.mvr.2025.104876","DOIUrl":"10.1016/j.mvr.2025.104876","url":null,"abstract":"<div><h3>Purpose</h3><div>Taurine exists abundantly in the retina and plays a vital role in retinal function. Monocarboxylate transporter 7 (MCT7) is found as a facilitative taurine transporter; however, its involvement in taurine dynamics in the retina is not yet fully understood. The purpose of the present study is to clarify the protein expression and function of MCT7 in retinal cells.</div></div><div><h3>Methods</h3><div>Guinea pig antibodies were raised against the amino acid residues of rat MCT7, and immunostaining was performed to clarify protein expression in the rat retina. To characterize taurine influx into retinal pericytes, a [³H]taurine transport assay was conducted using TR-rPCT1 cells, immortalized rat retinal pericytes. A knockdown assay using MCT7 small interfering RNA (siRNA) was performed to examine the involvement of MCT7 in taurine efflux in TR-rPCT1 and immortalized rat retinal capillary endothelial (TR-iBRB2) cells.</div></div><div><h3>Results</h3><div>The MCT7 protein expression was observed throughout the retinal layer. Immunostaining of isolated retinal capillaries revealed MCT7 expression in retinal pericytes and capillary endothelial cells. [³H]Taurine influx transport in TR-rPCT1 cells depends on temperature, concentration (<em>K</em>_m = 11.2 μM), and extracellular Na⁺ and Cl⁻, and was inhibited by substrates for taurine transporter (TauT), suggesting the involvement of TauT in taurine influx in retinal pericytes. Moreover, MCT7 siRNA decreased MCT7 expression and [³H]taurine efflux in TR-rPCT1 and TR-iBRB2 cells, suggesting that the taurine efflux transport involves MCT7 at least partly.</div></div><div><h3>Conclusions</h3><div>The present study revealed that MCT7 functions as a taurine efflux transporter in both retinal pericytes and capillary endothelial cells.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"163 ","pages":"Article 104876"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102683","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}