Microvascular Research[JOURNAL]
Sun
200 papers
Impact of the menstrual cycle phase on microvascular function at high altitude.
Tagliapietra G, Manferdelli G, Citherlet T … +4 more , Raberin A, Narang BJ, Debevec T, Millet GP
Microvasc Res · 2026 Mar · PMID 41397533 · Publisher ↗
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 inv...
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 O 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; p = 0.920), normalized reperfusion slope (0.013 ± 0.010 vs. 0.014 ± 0.005 %·s; 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.
Vascular diameter and responsiveness to soluble guanylate cyclase modulators: A systematic review of preclinical and clinical evidence.
Josef MS
Microvasc Res · 2026 Mar · PMID 41365429 · Publisher ↗
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. Under...
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.
Fifteen-minute walk improves microcirculation in people with diabetes mellitus.
Palacios-Abril L, Tardáguila-García A, Álvaro-Afonso FJ … +3 more , Tejeda-Ramírez S, López-Moral M, Lázaro-Martínez JL
Microvasc Res · 2026 Mar · PMID 41360181 · Publisher ↗
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...
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.
Pericytes at the crossroads of sepsis: Mechanisms and therapeutic opportunities in vascular barrier dysfunction.
Miao C, Xiao L, Xu X … +3 more , Miao J, Liu J, Zhao H
Microvasc Res · 2026 Mar · PMID 41349792 · Publisher ↗
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 associate...
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.
The underdiagnosed risk of Coronary microvascular dysfunction in post CABG/angioplasty patients a call for myocardial perfusion mapping of blood flow dynamics.
Gayathri B, Sreekanth K, Aparna G … +3 more , Chandana C, Radhakrishnan N, Radhakrishnan EK
Microvasc Res · 2026 Mar · PMID 41308870 · Publisher ↗
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 p...
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.
Chronic nicotine exposure drives dose-dependent pulmonary hypertension and cardiopulmonary remodeling: Preclinical and clinical validation.
Zhou J, Hou X, Zheng Z … +8 more , Quan T, Meng X, Xu Y, Zhao L, Ren X, Yang L, Shi Y, Qin X
Microvasc Res · 2026 Jan · PMID 41242379 · Publisher ↗
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 clos...
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 (R = 0.8553, P < 0.01) and negatively with TAPSE (R = 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.
PAI-1 promotes thromboangiitis obliterans progression through NF-κB-NLRP3 pathway activation via HIF-1α-dependent signaling.
Xu X, Ge X, Ci H … +4 more , Abulaihaiti M, Yang J, Li Y, Zhu F
Microvasc Res · 2026 Jan · PMID 41238034 · Publisher ↗
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 understoo...
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.
Mechanistic investigation of quercetin (an active component of RAS-RH) in modulating radiation-induced coronary microvascular dysfunction via the TCs-ECs crosstalk pathway.
Hugang J, Ai L, Zeao G … +5 more , Chunzhen R, Wenyan L, Kai L, Xinke Z, Yingdong L
Microvasc Res · 2026 Jan · PMID 41203067 · Publisher ↗
BACKGROUND: Coronary Microvascular Dysfunction (CMVD), a prevalent comorbidity of various cardiovascular diseases, may contribute to myocardial cell ischemic necrosis. The loss of microvessels-driven by endothelial cells...
BACKGROUND: Coronary Microvascular Dysfunction (CMVD), a prevalent comorbidity of various cardiovascular diseases, may contribute to myocardial cell ischemic necrosis. The loss of microvessels-driven by endothelial cells (ECs) apoptosis-is the core pathological hallmarks of CMVD. Our previous studies have established that RAS-RH (Angelica sinensis and Astragalus membranaceus ultrafiltrate) promotes angiogenesis and improves cardiac perfusion. However, its underlying molecular mechanisms remain incompletely understood. PURPOSE: This study aimed to elucidate the key mechanism by which quercetin, the primary active component of RAS-RH, modulates radiation-induced ECs apoptosis. METHODS: Through the integration of network pharmacology and transcriptomics, we identified potential active components of RAS-RH and their key targets involved in regulating the telocytes-endothelial cell (TCs-ECs) crosstalk pathway underlying CMVD. These predictions were further validated using in vitro cellular models via flow cytometry, western blot, wound-healing assays, in situ hybridization, immunofluorescence staining, and EdU proliferation assays. RESULTS: Consistent with our predictions, experimental results demonstrated that quercetin (the primary active component of RAS-RH) significantly upregulated the expression of HIF-1α and miRNA-126 in TCs (P < 0.01) and enhanced miRNA-126 paracrine secretion. Through this paracrine mechanism, quercetin downregulated the expression of Cypd, ANT, F1F0-ATPase, and VDAC in ECs (P < 0.01), inhibited the reduction of mitochondrial membrane potential (ΔΨm) and ECs apoptosis induced by excessive mPTP opening. Collectively, these effects enhanced ECs proliferation, migration, and tube formation capacity, ultimately promoting angiogenesis. CONCLUSION: These results collectively demonstrate that quercetin, the primary active component of RAS-RH, suppresses excessive mPTP activation and apoptosis while stimulating ECs migration and tube formation. This occurs via upregulating HIF-1α and miRNA-126 expression in TCs and enhancing miRNA-126 paracrine to ECs, positioning the TCs-ECs crosstalk mechanism as a promising novel therapeutic target for intervening in coronary microcirculation dysfunction.
DOT1L-mediated H3K79me1 transcriptional activation of Acp5 aggravates inflammatory responses following diabetic vascular injury.
Zhang J, Yang Z, Liu L … +9 more , Wu D, Cheng C, Zhu P, Wang W, Li W, Deng H, Ma Y, Huang C, Yang J
Microvasc Res · 2026 Jan · PMID 41187901 · Publisher ↗
BACKGROUND: 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...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Effects of semaglutide on vessel morphology: Studies on the chicken chorioallantoic membrane.
Chen PH, Abood S, Bloom S
Microvasc Res · 2026 Jan · PMID 41125168 · Full text
Glucagon-Like Peptide-1 (GLP-1) receptor agonists are widely used to manage type 2 diabetes and promote weight loss. Semaglutide (SEM)-a long acting GLP-1-has experienced an extraordinary surge in popularity since its ap...
Glucagon-Like Peptide-1 (GLP-1) receptor agonists are widely used to manage type 2 diabetes and promote weight loss. Semaglutide (SEM)-a long acting GLP-1-has experienced an extraordinary surge in popularity since its approval in 2017. Between 2021 and 2023, SEM prescription fills in the U.S. climbed to 2.56 million per month. Yet, the uptake of SEM into larger populations has raised safety concerns, with provocative findings now suggesting that SEM could negatively affect ocular and reproductive systems, counter to its beneficial effects on the heart. At least some of these concerns involve SEMs ability to alter vascular morphology in these organs. Herein, we study the impact of SEM on vasculature using the well-established chicken chorioallantoic membrane (CAM). This in vivo model mimics vascular beds found in the human eye and placenta and can approximate the effects of drugs on these organs. The CAM also responds to vasoactive drugs in a similar way to the coronary arteries of the heart. Hence, the CAM provides a convenient system to simultaneously interrogate the impact of SEM on ocular, reproductive, and coronary vascular biology. Our studies show that SEM causes vessels to develop with fewer branching points, yielding longer and more direct connections, that shift local blow flow patterns. However, these changes are only significant at SEM concentrations well above the therapeutic dose.
Clinical profile and long-term outcomes of chest pain patients with coronary microvascular dysfunction from the emergency department - results from the Yale-CMD registry.
Safdar B, Zhou B, Li F … +8 more , Camici PG, Dziura J, Jastreboff AM, Lansky A, Shah SM, Sinusas A, Spatz E, D'Onofrio G
Microvasc Res · 2026 Jan · PMID 41110546 · Full text
OBJECTIVE: 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, myoc...
OBJECTIVE: 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. METHODS: 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 <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. RESULTS: 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). CONCLUSIONS: 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.
Invasive coronary physiology assessment and predictors of coronary microvascular dysfunction in patients with diabetes mellitus.
Benedetti A, Bringmans T, Vanhaverbeke M … +12 more , Mathieu FD, Palmers PJ, Coussement P, De Wilder K, Everaert B, Coeman M, Demeure F, Kersemans M, Kayaert P, Argacha JF, Segers VFM, Zivelonghi C
Microvasc Res · 2026 Jan · PMID 41110545 · Publisher ↗
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 pr...
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.
The association between cutaneous microvascular dysfunction and pulmonary artery hemodynamics in heart transplant candidates.
Fatorelli AF, Tibirica E, Kasal DAB
Microvasc Res · 2026 Jan · PMID 41043296 · Publisher ↗
Abstract loading — click title to view on PubMed.
Association between posterior vitreous detachment stage and quantitative neovascularization morphology in proliferative diabetic retinopathy using wide-field swept-source optical coherence tomography angiography.
Xu Z, Chen R, Li J … +9 more , Huang D, Li T, Liang H, Xu Z, Huang J, Gui M, Hojas IM, Zhuang X, Zhang L
Microvasc Res · 2026 Jan · PMID 40975515 · Publisher ↗
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) acro...
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.
Involvement of monocarboxylate transporter 7 in taurine efflux transport from rat retinal pericytes and capillary endothelial cells.
Tega Y, Kusakabe F, Akanuma SI … +1 more , Hosoya KI
Microvasc Res · 2026 Jan · PMID 40975514 · Publisher ↗
PURPOSE: 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 dynami...
PURPOSE: 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. METHODS: 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 [H]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. RESULTS: 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. [H]Taurine influx transport in TR-rPCT1 cells depends on temperature, concentration (K = 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 [H]taurine efflux in TR-rPCT1 and TR-iBRB2 cells, suggesting that the taurine efflux transport involves MCT7 at least partly. CONCLUSIONS: The present study revealed that MCT7 functions as a taurine efflux transporter in both retinal pericytes and capillary endothelial cells.
Nailfold video capillaroscopy predicts severe progression at three years in systemic sclerosis: Results from SCLEROCAP study.
Boulon C, Larrouture I, Blaise S … +23 more , Mangin M, Chevoir JD, Senet P, Lazareth I, Baudot N, Tribout L, Imbert B, Lapébie FX, Lacroix P, Truchetet ME, Seneschal J, Solanilla A, Lazaro E, Quéré I, Pistorius MA, Le Hello C, Lhomme E, Perez P, Picard F, Blanchard E, Carpentier P, Dari L, Constans J
Microvasc Res · 2026 Jan · PMID 40967366 · Publisher ↗
OBJECTIVES: Systemic sclerosis (SSc) has a variable evolution but may be life-threatening owing to pulmonary, cardiac or renal involvement. Nailfold video capillaroscopy (NVC) is abnormal early in the disease and is cruc...
OBJECTIVES: Systemic sclerosis (SSc) has a variable evolution but may be life-threatening owing to pulmonary, cardiac or renal involvement. Nailfold video capillaroscopy (NVC) is abnormal early in the disease and is crucial for diagnosis. An association between subtypes of scleroderma pattern and disease progression has been suggested. Therefore, we conducted a prospective study to assess whether capillaroscopy can identify SSc patients at risk of progression. METHODS: SCLEROCAP was a prospective multicentre observational study that included patients with a diagnosis of SSc followed up for three years. Each patient had yearly standard evaluation and NVC. Images were read by two observers blinded from each other and were classified into subtypes (2 for Maricq's and 3 for Cutolo's classification). Severe progression was defined as cardiac, pulmonary or renal involvement or progression and was assessed by a validation committee. RESULTS: Three hundred and eighty-seven patients were included of whom 369 were followed-up and 53 (14 %) had severe progression. A simple model using Cutolo's capillaroscopic late stage, short duration of disease and age was as powerful in predicting severe progression as a model using all the parameters known to be predictive (AUC[95 %CI] 0.74[0.67-0.82] vs 0.73[0.64-0.77] respectively. CONCLUSION: NVC is a predictor of severe progression and might be helpful for early therapeutic decisions in patients with SSc.
Retinal neurodegeneration and choroidal changes of early diabetes in peripapillary region detected by swept-source optical coherence tomography angiography.
Zheng Z, Liu N, Wang J … +4 more , Zhang Y, Gu X, Song S, Yu X
Microvasc Res · 2026 Jan · PMID 40939765 · Publisher ↗
PURPOSE: This study was designed to evaluate peripapillary retinal nerve fiber layer (pRNFL) and choroidal alterations in diabetic patients without diabetic retinopathy (NDR), and further explore their association utiliz...
PURPOSE: This study was designed to evaluate peripapillary retinal nerve fiber layer (pRNFL) and choroidal alterations in diabetic patients without diabetic retinopathy (NDR), and further explore their association utilizing ultrawide-field swept-source optical coherence tomography angiography (UWF-SS-OCTA). METHODS: This cross-sectional study included 169 eyes of 169 NDR subjects and 54 eyes of 54 healthy controls. pRNFL, choroidal thickness and volume were compared and measured with UWF-SS-OCTA. The association between pRNFL and choroidal parameters was assessed with Spearman correlation analysis. Further multivariate linear regression analysis was performed to evaluate their relationship after adjusting for confounding factors. RESULTS: Compared with healthy controls, NDR patients showed reduced choroidal thickness and volume in the full range and several peripapillary subfields, while a statistical decrease of pRNFL was only detected in the inferior quadrant (P = 0.04). Regarding the distribution profiles in the peripapillary region, the choroid was thickest in the temporal region and thinnest in the inferior region, and a more prominent decrease compared with controls was found in the inferior region. Average pRNFL thickness was independently associated with full-range mean choroidal volume in multiple regression analysis (β = 0.16, P = 0.04). CONCLUSION: As two early signs of DR, choroidal thinning could precede retinal neurodegeneration. Decreased choroidal thickness may account for the susceptibility of RNFL thinning.
Sex differences in near-infrared spectroscopy reactive hyperemia: Influence of adipose tissue and desaturation rate.
Chatlaong MA, Dowell HC, Smith OJ … +1 more , Jessee MB
Microvasc Res · 2026 Jan · PMID 40925504 · Publisher ↗
UNLABELLED: 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...
UNLABELLED: 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. METHODS: 23 female and 22 male participants completed forearm and thigh vascular occlusion tests. ATT was measured via ultrasound. Reperfusion slopes (StO%/s) were compared between sexes using linear models with and without desaturation slope (StO%/s) and ATT as covariates. Results are mean or mean difference [95 % CI]. RESULTS: In both limbs, females had greater ATT (p < 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], p < 0.001) but not the arm (females = 1.60 [1.36, 1.84], males = 1.57 [1.29, 1.86], p = 0.874). Sex differences were not observed in adjusted models (both p ≥ 0.631). ATT and desaturation slope explained unique variance in the leg (both p ≤ 0.001), but only desaturation slope did in the arm (p < 0.001). CONCLUSION: 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.
Histamine induces vascular endothelial cell proliferation via the histamine H1 receptor-extracellular regulated protein kinase 1/2-cyclin D1/cyclin-dependent kinase 4/6 axis.
Wake H, Hatipoglu OF, Nishinaka T … +5 more , Watanabe M, Toyomura T, Mori S, Nishibori M, Takahashi H
Microvasc Res · 2026 Jan · PMID 40912453 · Publisher ↗
Histamine is a biogenic amine that plays important roles in the inflammatory phase of physiological wound healing and proliferation of normal and tumor cells. Stimulation of the histamine H1 receptor induces vascular end...
Histamine is a biogenic amine that plays important roles in the inflammatory phase of physiological wound healing and proliferation of normal and tumor cells. Stimulation of the histamine H1 receptor induces vascular endothelial cell proliferation, possibly contributing to angiogenesis during wound healing and cancer development. However, the specific signaling pathways involved in angiogenesis remain unclear. Based on our previous report that histamine induces endothelial cell tube formation by increasing the vascular endothelial growth factor and matrix metalloproteinase levels via the H1 receptor, we aimed to further examine histamine-induced cell proliferation using EA.hy926 vascular endothelial cells in this study. Histamine phosphorylated extracellular regulated protein kinase-1/2 through the protein kinase C pathway via the H1 receptor and increased c-Fos expression via phosphorylation of Elk-1 and CRE-binding protein. Moreover, c-Fos formed activator protein-1, which further upregulated cyclin D1 expression. Cyclin D1 formed a complex with cyclin-dependent kinase-4/6 and phosphorylated Rb, causing the transcription factor E2F, which is bound to Rb, to dissociate from Rb and induce the factors important for S phase initiation that advance the cell cycle. Overall, our findings in this study to identify H1 receptor-mediated cell proliferation signals in endothelial cells using histamine can aid in the development of new strategies for wound healing and cancer treatment.
Shear stress-activated MMP-2 promotes BMSCs migration via the LIMK1/Cofilin axis during vascular remodeling.
Liang Y, Wu J, Fang X … +4 more , Chang Y, Tang Y, Diao G, Yin C
Microvasc Res · 2025 Nov · PMID 40882768 · Publisher ↗
Shear stress enhances matrix metalloproteinase-2 (MMP-2) expression, which plays a critical role in bone marrow mesenchymal stem cells (BMSCs) migration and vascular remodeling via microenvironmental interactions with mo...
Shear stress enhances matrix metalloproteinase-2 (MMP-2) expression, which plays a critical role in bone marrow mesenchymal stem cells (BMSCs) migration and vascular remodeling via microenvironmental interactions with mouse aortic endothelial cells (MAECs). MAECs were exposed to disturbed flow using a custom flow device for 1, 3, or 5 h, and conditioned media (MAEC-CM) were collected. BMSCs migration in response to different MAEC-CM conditions was assessed by flow cytometry, transwell, and wound-healing assays. MMP-2 levels in MAEC-CM were modulated with recombinant protein or neutralizing antibody. LIMK1/Cofilin pathway activation was evaluated by western blot, and the LIMK1 inhibitor BMS-3 was used to confirm pathway function. Disturbed flow altered MAECs density, morphology, and intercellular gaps, with apoptosis increasing over time. ELISA showed MMP-2 secretion peaked at 3 h, coinciding with maximal BMSCs migration. Recombinant MMP-2 (400 ng/mL) further enhanced, while MMP-2 neutralizing antibody (100 ng/mL) suppressed, migration induced by MAEC-CM-3 h. Western blot revealed significant phosphorylation of LIMK1 and Cofilin after MAEC-CM-3 h treatment, with higher levels in recombinant MMP-2-treated groups compared to neutralization. BMS-3 significantly reduced MMP-2-induced BMSCs migration and phosphorylation of LIMK1/Cofilin without affecting total protein levels. These results indicate that shear stress-induced MMP-2 promotes BMSCs motility through LIMK1-dependent Cofilin activation. This study not only clarifies the molecular mechanism by which disturbed flow regulates BMSCs migration but also provides a theoretical basis for BMSC-mediated vascular repair, offering potential targets for future clinical applications.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe