Microvascular Research[JOURNAL]
Sun
200 papers
Association between retinal microcirculation and cardiac function: A cross-sectional study using OCTA.
Zhang Y, Sun R, Yang S … +3 more , Xu N, Lu L, Cao M
Microvasc Res · 2026 Jun · PMID 42372861 · Publisher ↗
AIM: To investigate the association between retinal microcirculation and cardiac function using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional study, 78 participants who underwent both...
AIM: To investigate the association between retinal microcirculation and cardiac function using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional study, 78 participants who underwent both OCTA and transthoracic echocardiography were included. OCTA was used to quantify vessel density (VD) and perfusion density (PD) in the optic disc region. Cardiac function parameters, including left ventricular ejection fraction (EF), mitral valve E wave (MV-E), and A wave (MV-A), were obtained via echocardiography. Correlation analyses and univariate and multivariable linear regression models were applied to evaluate associations between retinal microvascular metrics and cardiac function. RESULTS: Retinal VD and PD in all regions showed significant positive correlations with EF, indicating that better cardiac systolic function is associated with higher microvascular density and perfusion. MV-E, reflecting early diastolic function, was also positively correlated with inner and whole retinal VD and PD, whereas MV-A showed no significant association. Multivariable regression confirmed that EF and MV-E were independent positive determinants of whole VD and PD, while cerebrovascular disease was independently associated with reduced retinal microcirculation. Age demonstrated a negative association with VD. CONCLUSION: Retinal microcirculation is closely linked to both systolic and diastolic cardiac function. OCTA-derived parameters, particularly VD and PD, may provide a non-invasive and quantitative approach for assessing systemic cardiovascular status and hold potential may serve as potential indicators of cardiovascular dysfunction.
Microvascular dysfunction and neurovascular signalling impairment in diabetic silent myocardial ischemia.
Rajasekaran HK
Microvasc Res · 2026 Jun · PMID 42324025 · Publisher ↗
Diabetic silent myocardial ischemia (DSMI) represents a clinically underappreciated yet life-threatening cardiovascular complication in which impaired myocardial perfusion occurs without recognisable symptoms. Two conver...
Diabetic silent myocardial ischemia (DSMI) represents a clinically underappreciated yet life-threatening cardiovascular complication in which impaired myocardial perfusion occurs without recognisable symptoms. Two converging pathological axes underlie this phenotype: coronary microvascular dysfunction and neurocardiac signalling disruption. Chronic hyperglycaemia drives oxidative stress, advanced glycation end-product (AGE) accumulation, and mitochondrial dysfunction in endothelial and smooth-muscle cells, collectively impairing nitric oxide (NO) bioavailability, coronary flow reserve, and capillary integrity. Simultaneously, diabetic peripheral and autonomic neuropathy attenuates nociceptive transmission and disrupts neurovascular coupling, blunting the perception of ischaemic pain. At the molecular level, dysregulated insulin receptor (INSR), angiotensin II type 1 receptor (AT1R), toll-like receptor 4 (TLR4), AMP-activated protein kinase (AMPK), and transient receptor potential (TRP) channel signalling converge to perpetuate endothelial injury, vascular inflammation, and neural dysfunction. Critically, emerging evidence implicates mitochondrial reactive oxygen species (mtROS) overproduction, impaired mitochondrial biogenesis, and altered mitochondrial dynamics as shared mechanistic nodes linking both axes. This review synthesises current mechanistic knowledge within a novel unified framework, proposes candidate biomarkers including urinary 8-OHdG, NT-proBNP, heart rate variability indices, and coronary flow reserve by cardiac PET/CMR and identifies actionable therapeutic targets, including mitochondria-directed antioxidants (MitoQ, SS-31), SGLT2 inhibitors, GLP-1 receptor agonists, TLR4 antagonists, and TRPV1 modulators. Testable mechanistic hypotheses and directions for future translational research are proposed to accelerate early diagnosis and disease-modifying intervention in high-risk diabetic patients.
Association of circulating biomarkers of glycocalyx injury, sirtuin 1, and NFκB p65 in individuals with type 2 diabetes and concurrent arterial hypertension.
Viudes DR, Mateus AR, Silva CA … +1 more , do Carmo Franco M
Microvasc Res · 2026 Jun · PMID 42320824 · Publisher ↗
PURPOSE: Type 2 diabetes (T2D) and arterial hypertension are major cardiovascular risk factors, with endothelial dysfunction being a central pathological mechanism. This study investigated the concurrent T2D and arterial...
PURPOSE: Type 2 diabetes (T2D) and arterial hypertension are major cardiovascular risk factors, with endothelial dysfunction being a central pathological mechanism. This study investigated the concurrent T2D and arterial hypertension on plasma levels of endothelial glycocalyx components and inflammatory/vasoprotective markers. METHODS: In this cross sectional study, we assessed 68 individuals (44 female and 24 male) aged 41-69 years. Thirty-one individuals had T2D and thirty-seven had concurrent T2D and arterial hypertension. Anthropometry parameters and biomarkers profile were evaluated. Plasma syndecan-1, syndecan-4, hyaluronic acid, NFκB p65, and sirtuin 1 were measured using ELISA assay. RESULTS: Our findings revealed that individuals with coexisting hypertension and T2D exhibited significantly elevated hyaluronic acid (p = 0.013), syndecan-4 (p = 0.028), and NFκB p65 (p = 0.002), and markedly reduced sirtuin 1 (p = 0.007), compared to T2D-only participants. Effect size analysis showed moderate effect magnitudes for hyaluronic acid (Ƞp = 0.10), syndecan-4 (Ƞp = 0.10), NFκB p65 (Ƞp = 0.14), and sirtuin 1 (Ƞp = 0.11). In unadjusted analyses, sirtuin 1 was inversely correlated with hyaluronic acid (rho = -0.259; p = 0.033), syndecan-4 (rho = -0.307; p = 0.011), and NFκB p65 (rho = -0.276; p = 0.023), whereas hyaluronic acid was positively correlated with syndecan-4 (rho = 0.359; p = 0.003). After adjustment for diabetes duration, the associations of hyaluronic acid with syndecan-4 and of sirtuin 1 with NFκB p65 remained significant, whereas the correlations of sirtuin 1 with hyaluronic acid and syndecan-4 were no longer significant. CONCLUSION: Our results suggest that the coexistence of T2D and arterial hypertension is associated with unfavorable vascular biomarker profile, characterized by glycocalyx injury, greater inflammatory activation, and reduced vasoprotective signaling.
Targeting miR-10 alleviates atherosclerosis by enhancing intestinal ABCA1-mediated cholesterol efflux and repairing intestinal barrier.
Yang Y, Gao Z, Xiao Q … +8 more , Lian S, Chen J, Su W, Zhang Y, Deng S, Zhao K, He J, Liu C
Microvasc Res · 2026 Jun · PMID 42303178 · Publisher ↗
BACKGROUND AND AIMS: HDL biogenesis is mainly determined by intestinal and hepatic ABCA1. Inhibiting miR-10b increases macrophage ABCA1 but does not affect intestinal/hepatic ABCA1 or plasma HDL cholesterol in ApoE mice....
BACKGROUND AND AIMS: HDL biogenesis is mainly determined by intestinal and hepatic ABCA1. Inhibiting miR-10b increases macrophage ABCA1 but does not affect intestinal/hepatic ABCA1 or plasma HDL cholesterol in ApoE mice. Given that miR-10a and miR-10b (with similar seed sequences) are comparably expressed in intestine/liver, we hypothesize they redundantly regulate intestinal/hepatic ABCA1 and HDL biogenesis. METHODS: Primary mouse enterocytes and hepatocytes were treated with antagonist miR-10a, antagonist miR-10b, or their combination, followed by systemic inhibition studies in ApoE and C57BL/6 J mice. ABCA1 expression (qPCR/Western blot) and cholesterol efflux to ApoA-I/HDL were measured. Additionally, atherosclerotic lesions and HDL biogenesis in mice were assessed; ApoE/ mice were further tested for intestinal barrier (intestinal permeability) and systemic inflammation (gut microbiota, inflammatory responses). RESULTS: Combined, not individual, miR-10a/b inhibition upregulated ABCA1 and increased cholesterol efflux in primary mouse enterocytes. Consistently, in ApoE and wild-type C57BL/6J mice, combined miR-10 inhibition upregulated intestinal ABCA1, promoted HDL biogenesis, enhanced cholesterol efflux, and ultimately exerted anti-atherosclerotic effects. Concurrently, this dual inhibition reduced intestinal cholesterol accumulation, reshaped gut microbiota, and restored intestinal barrier integrity. Specifically, 16S rRNA sequencing shows that miR-10 inhibition decreased Proteobacteria (phylum level), while it increased Bacteroidetes (phylum level) and enriched Bifidobacterium and Lactobacillus (genus level). These effects collectively suppress systemic inflammation and exert anti-atherosclerotic effects in ApoE mice. Additionally, miR-10 inhibition alleviated systemic inflammation in ApoE mice by suppressing TLR4/NLRP3 inflammasome activation, with this suppression further verified in vitro. CONCLUSIONS: Inhibition of miR-10 attenuates atherosclerosis through enhanced intestinal ABCA1-mediated cholesterol efflux and barrier integrity, paralleling a favorable shift in gut microbiota composition particularly the enrichment of Bifidobacterium and Lactobacillus. This coordinated intestinal improvement reduces systemic inflammation and ultimately suppresses TLR4/NLRP3 inflammasome activation.
The effect of acute high-intensity interval exercise on microvascular function and local skeletal muscle oxygenation.
Nikolovski N, Di Salvo AN, Estafanos S … +3 more , Bailleul C, Gillen JB, Bentley RF
Microvasc Res · 2026 Jun · PMID 42289233 · Publisher ↗
High-intensity interval exercise (HIIE) improves cardiorespiratory fitness through cardiac and skeletal muscle adaptations; however, the relationship between microvascular function and local skeletal muscle oxygenation d...
High-intensity interval exercise (HIIE) improves cardiorespiratory fitness through cardiac and skeletal muscle adaptations; however, the relationship between microvascular function and local skeletal muscle oxygenation during HIIE is unclear. Near-infrared spectroscopy at the vastus lateralis (∆ from baseline) was used to assess microvascular function pre- and post-HIIE and oxygenation throughout HIIE (n = 22 enrolled; n = 19 reported with complete oxygenation data, 27 ± 6 yrs., 42% female). HIIE consisted of twelve, 1-min intervals at 85% of peak power output while microvascular function was assessed using vascular occlusion-reperfusion. During HIIE, despite no change in the deoxygenation time constant tau (τ) (all p > 0.059), deoxygenation magnitude progressively increased at intervals 6 and 8 (both p < 0.011) and was greater at interval 11 compared to 1 (-49 ± 13 vs. -41 ± 19%, p = 0.033). Similarly, there was no change in the reoxygenation τ (all p > 0.753) while reoxygenation magnitude was immediately attenuated from interval 2 compared to 1 (-14 ± 18 vs. -6 ± 12%, p = 0.007) and was less at both intervals 6 and 11 compared to 1 (both p < 0.004). Microvascular function assessed as the 2-min hypersaturation area under the curve (AUC) was lower 15 min post- and 2 h post-HIIE compared to pre-exercise (both p ≤ 0.025), while the 10 s saturation upslope remained unchanged when controlling for the occlusion nadir (p = 0.212). The 2-min AUC (ρ = 0.659, p = 0.003) and 10 s upslope (r = 0.481, p = 0.043) correlated with peak cardiorespiratory fitness but were not related to reoxygenation outcomes (all p ≥ 0.113). These findings describe the acute oxygenation environment of HIIE while suggesting that sustained microvascular vasodilation may be lower post-HIIE.
RNF213 deficiency in human iPSC-derived vascular organoids captures key feature of moyamoya disease vasculopathy.
Wu M, Li S, Liu W … +3 more , Guo Z, Guo Z, Zhang D
Microvasc Res · 2026 Jun · PMID 42289232 · Publisher ↗
OBJECTIVES: This study aimed to establish a human iPSC-derived model of Moyamoya disease (MMD) by generating RNF213-knockdown vascular organoids to capture key disease-relevant vascular features. METHODS: RNF213-knockdow...
OBJECTIVES: This study aimed to establish a human iPSC-derived model of Moyamoya disease (MMD) by generating RNF213-knockdown vascular organoids to capture key disease-relevant vascular features. METHODS: RNF213-knockdown iPSC lines were established using lentiviral shRNA and selected with puromycin. Knockdown efficiency was validated by qRT-PCR and Western blot. Vascular organoids were differentiated from the engineered iPSCs using the STEMdiff™ Blood Vessel Organoid Kit according to the manufacturer's protocol. Organoids were analyzed by immunofluorescence for vascular markers (CD31, COL4A1, PDGFR-β, α-SMA) and transcriptomic profiling was performed using DRUG-seq. RESULTS: Three distinct RNF213-knockdown iPSC clones were successfully generated, exhibiting varying knockdown efficiencies. qPCR analysis demonstrated RNF213 mRNA reductions of approximately 22% (V1), 70% (V2), and 88% (V3), with corresponding decreases in protein levels confirmed by Western blot. Although V2 and V3 clones displayed more substantial molecular knockdown, organoids derived from the V1 clone manifested the most severe phenotypic abnormalities, characterized by disrupted CD31 endothelial networks and Collagen IV basement membranes. Transcriptomic profiling identified 1543 differentially expressed genes, with enrichment analysis revealing significant dysregulation of angiogenesis-related pathways. This included marked upregulation of pro-angiogenic factors (CCL5, EREG) and downregulation of inhibitory factors (TNMD), effectively recapitulating key molecular features of Moyamoya disease. CONCLUSION: We developed a novel human vascular organoid model with RNF-213 deficiency that captures key features of MMD vasculopathy, providing a valuable platform for mechanistic studies and drug screening.
Microvascular remodeling in the carotid body of spontaneously hypertensive rats: A stereological study.
Ivanov AV, Atanasova DY, Lazarov NE
Microvasc Res · 2026 Jun · PMID 42264328 · Publisher ↗
The carotid body (CB) serves as the primary peripheral arterial chemoreceptor in mammals and plays a key role in the regulation of blood pressure by sensing changes in arterial blood gas levels and influencing sympatheti...
The carotid body (CB) serves as the primary peripheral arterial chemoreceptor in mammals and plays a key role in the regulation of blood pressure by sensing changes in arterial blood gas levels and influencing sympathetic nerve activity. It is one of the most highly vascularized organs, with blood vessels occupying approximately 25% of its volume. Although hypertensive conditions are known to induce CB structural plasticity, detailed morphometric analysis of its vasculature remains limited. We performed a quantitative stereological study to assess microvascular remodeling in the CB of spontaneously hypertensive rats (SHR) compared to normotensive Wistar rats (NWR). High-resolution electron microscopy was used to visualize the vascular architecture of the hypertensive CB, and stereological techniques were applied to estimate the total length of its capillary network and the cross-sectional area of one capillary. We found that the total capillary length in the CB of SHR (10.66 ± 0.60 mm) is twice the one in NWR (5.36 ± 0.36 mm). Conversely, the average capillary cross-sectional area was significantly reduced in SHR (20.6 ± 1.14 μm) versus NWR controls (57.80 ± 1.23 μm), indicating a denser capillary network in the hypertensive CB. Our findings demonstrate pronounced microvascular remodeling in the hypertensive CB of rats, characterized by an elongated capillary network. Such changes reflect a hypervascular state that may facilitate enhanced chemoreflex sensitivity. This study provides quantitative evidence supporting the role of CB vasculature in hypertensive pathophysiology and highlights its potential as a target for therapeutic modulation.
Serial CO₂ hand baths are associated with improved microvascular parameters and Raynaud-related symptoms in systemic sclerosis: A controlled feasibility study.
Schulz N, Müller-Ladner U, Lange U … +1 more , Klemm P
Microvasc Res · 2026 Jun · PMID 42264327 · Publisher ↗
BACKGROUND: Raynaud's phenomenon (RP) in systemic sclerosis (SSc) is driven by microvascular dysfunction. Previous work showed acute hemodynamic improvement after a single CO₂ hand bath in SSc. We investigated the effect...
BACKGROUND: Raynaud's phenomenon (RP) in systemic sclerosis (SSc) is driven by microvascular dysfunction. Previous work showed acute hemodynamic improvement after a single CO₂ hand bath in SSc. We investigated the effects of serial CO₂ hand baths on blood flow and symptom burden. METHODS: In this controlled feasibility study, fourteen patients with SSc and severe RP and fourteen age-matched healthy controls underwent daily CO₂ hand baths for 7 consecutive days. Primary endpoint was change in Doppler-derived resistance index (RI) from baseline to day 7 (both groups). Secondary endpoints included Raynaud Condition Score (RCS), attack frequency and duration. RESULTS: Baseline RI was significantly higher in SSc than in healthy controls (0.80 ± 0.02 vs. 0.73 ± 0.03, p < 0.001). Following intervention, RI decreased significantly in both groups (SSc: mean change -0.17, 95% CI [-0.20,-0.13], p < 0.001, controls: mean change -0.11, 95% CI [-0.13,-0.09], p < 0.001), with no significant between-group difference at day 7 (0.64 vs. 0.62, p = 0.889). In SSc, RCS improved progressively, exceeding the minimal clinical difference at day 4 (median change -1.6, p = 0.001) and reaching -3.0 points by day 7, with significant reductions in attack frequency and duration (both p ≤ 0.001). No adverse events occurred. CONCLUSION: Serial CO₂ hand baths were associated with progressive changes in Doppler-derived vascular parameters and patient-reported RP outcomes in SSc. Post-treatment RI values were comparable to those of healthy controls, and the minimal clinical difference was exceeded from day 4 onward. Randomized controlled trials are needed.
VAV3 is associated with atherosclerosis and ox-LDL-induced endothelial dysfunctional remodeling.
Wang G, Pu C, Li Q … +7 more , Liu Q, Wan X, Deng J, Dai M, Xie B, Huang L, Zhao Y
Microvasc Res · 2026 Jun · PMID 42248330 · Publisher ↗
BACKGROUND: Atherosclerosis is a major cause of ischemic stroke and is characterized by complex immune-metabolic dysregulation. VAV3, a Rho guanine nucleotide exchange factor, regulates multiple cellular processes, but i...
BACKGROUND: Atherosclerosis is a major cause of ischemic stroke and is characterized by complex immune-metabolic dysregulation. VAV3, a Rho guanine nucleotide exchange factor, regulates multiple cellular processes, but its role in vascular pathology remains unclear. This study aimed to explore the function and mechanism of VAV3 in atherosclerosis. METHODS: Transcriptomic datasets (GSE43292 and GSE28829) were analyzed to identify differentially expressed genes and disease-associated co-expression modules using weighted gene co-expression network analysis (WGCNA). The Boruta and LASSO algorithms were applied to screen for disease-associated signatures. Functional validation was performed in ox-LDL-stimulated HUVECs using VAV3 gain- and loss-of-function approaches. Assessments included cell proliferation, apoptosis, intracellular calcium accumulation, migration, lipid deposition, inflammatory factor secretion, and NF-κB pathway activation. In vivo validation was conducted in high-fat diet-fed APOE mice. RESULTS: Integrated transcriptomic analysis revealed concurrent immune activation and metabolic reprogramming in carotid plaques. WGCNA identified the MEgreen module as highly associated with atherosclerosis, and machine learning analyses selected CCR1 and VAV3 as public-dataset-derived candidate molecular signatures. In APOE mice, atherosclerotic lesions showed increased lipid deposition, elevated inflammatory mediators, and enhanced VAV3 expression. In ox-LDL-treated HUVECs, VAV3 overexpression further enhanced cell viability, proliferation, and migration, reduced apoptosis, and increased intracellular calcium accumulation and lipid deposition, indicating a shift toward an abnormal proliferative and apoptosis-resistant endothelial phenotype. In contrast, VAV3 knockdown attenuated these ox-LDL-induced abnormal changes and partially restored the cellular phenotype toward the control state. VAV3 modulation also altered GRB2 expression and p65 phosphorylation, accompanied by changes in IL-6, TNF-α, CRP, and Lp-PLA2 secretion. Co-IP further suggested an association between GRB2 and p-P65. These findings indicate that VAV3 may be associated with maladaptive endothelial remodeling and NF-κB-related inflammatory activation under ox-LDL stimulation. CONCLUSION: VAV3 is upregulated in atherosclerotic lesions and may contribute to ox-LDL-induced maladaptive endothelial remodeling, characterized by abnormal proliferation, apoptosis resistance, calcium accumulation, lipid deposition, and inflammatory activation. However, its clinical diagnostic value, therapeutic feasibility, and causal role in vivo require further validation.
Differential macro- and microvascular function responses to acute mental stress in healthy young men.
Kume D, Horiuchi M, Nishiwaki M
Microvasc Res · 2026 Jun · PMID 42229745 · Publisher ↗
Acute mental stress (MS) can impair macrovascular function, causing increased arterial stiffness and endothelial dysfunction; however, its effect on microvascular function remains largely unclear. This study examined the...
Acute mental stress (MS) can impair macrovascular function, causing increased arterial stiffness and endothelial dysfunction; however, its effect on microvascular function remains largely unclear. This study examined the impact of acute MS on microvascular function using near-infrared spectroscopy combined with vascular occlusion testing (NIRS-VOT). Seventeen healthy young men underwent two experimental trials with a randomized crossover design: control (CON) and MS trials. In the MS trial, the participants performed a 5-min MS task, whereas those in the CON trial remained quiet at rest for the same duration. Arterial stiffness was assessed using the cardio-ankle vascular index (CAVI). NIRS-VOT was conducted on the forearm, and the upslope of tissue oxygen saturation (StO) during the first 10 s after cuff release was used as an index of microvascular function. These measurements were obtained before (pre) and 30 min after (post) the task. The MS trial resulted in a significant increase (P < 0.05) in CAVI (pre: 6.0 ± 0.5 unit, post: 6.3 ± 0.6 unit), whereas no significant change was observed in the CON trial (pre: 6.0 ± 0.4 unit, post: 6.0 ± 0.5 unit). The StO upslope did not change significantly in either the CON (pre: 2.65 ± 0.99%/s, post: 2.72 ± 1.07%/s) or MS (pre: 2.64 ± 0.82%/s, post: 2.62 ± 0.70%/s) trial. The findings of this study demonstrate that acute MS increases arterial stiffness while having a limited impact on microvascular function, suggesting differential macro- and microvascular reactivity to acute MS.
Vasculitis-associated aberrant apolipoprotein A2 = VAP2 and SDF-1α in Kawasaki disease patients with coronary artery lesion.
Ebata R, Suzuki O, Uno K … +10 more , Kameoka Y, Hamano Y, Ito F, Murata S, Asano H, Matsushita K, Furuta S, Miki T, Hamada H, Suzuki K
Microvasc Res · 2026 May · PMID 42217821 · Publisher ↗
BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects the coronary arteries. The most serious complications are coronary artery lesions (CALs), including arterial dilatation, aneury...
BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects the coronary arteries. The most serious complications are coronary artery lesions (CALs), including arterial dilatation, aneurysm, and stenosis, which occur in approximately 25% of untreated patients. Intravenous immunoglobulin (IVIG) therapy markedly reduces the incidence of CALs to 2-3%; however, the underlying mechanisms of IVIG's therapeutic effects remain unclear. Recently, we identified a recombinant single-chain fragment of the variable region of human immunoglobulin G, termed VasSF, which significantly ameliorated vasculitis in SCG/Kj mice. The VasSF-binding protein of 24 kDa (VAP2) was subsequently identified as an aberrant form of apolipoprotein A2 (ApoA2) in the serum of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We investigated whether VAP2 and related ApoA2-derived molecules are associated with CAL formation in patients with KD. MATERIALS AND METHODS: Baseline demographic and clinical characteristics were evaluated in 34 patients with KD during the acute and convalescent phases. Among them, 14 (41.2%) were initial IVIG non-responders, and 10 (29.4%) developed CALs. RESULTS AND DISCUSSION: Western blot analysis revealed that VAP2 and VasSF bound to 17-kDa serum molecules predominantly during the acute phase of KD. Notably, in the CAL group, VAP2 levels exhibited a significant correlation with stromal cell-derived factor-1α (SDF-1α) (r = 0.5700, p = 0.049) among 78 cytokines analyzed. VAP2 was identified as a target molecule of VasSF in association with SDF-1α in our study. Considering that VasSF has been proposed as a therapeutic candidate for ANCA-associated vasculitis through targeting of aberrant ApoA2, VasSF may likewise represent a potential therapeutic agent for KD.
Mechanical stiffening and delayed cell death of endothelial cells exposed to impulsive pressure.
Nakadate H, Koike I, Nakamura S … +1 more , Aomura S
Microvasc Res · 2026 Jul · PMID 42214721 · Publisher ↗
Head impact induces rapid fluctuations in intracranial pressure, which are implicated in vascular damage even in the absence of skull fracture. Endothelial cells lining the inner lumen of blood vessels sense mechanical s...
Head impact induces rapid fluctuations in intracranial pressure, which are implicated in vascular damage even in the absence of skull fracture. Endothelial cells lining the inner lumen of blood vessels sense mechanical stimuli and transduce them into biological responses. We hypothesized that impact-induced pressure fluctuations alter endothelial cell mechanics and contribute to delayed endothelial injury. In this study, impulsive pressures with amplitudes and frequencies comparable to those generated during head impact were applied to cultured endothelial cells. Cellular stiffness was evaluated by measuring Young's modulus using atomic force microscopy, while mitochondrial membrane potential, caspase-3/7 activation, and cell viability were assessed using fluorescence imaging. Endothelial cells exposed to impulsive pressure showed a significant increase in stiffness after 1 h of loading, followed by mitochondrial membrane potential disruption after 3 h, caspase-3/7 activation after 6 h, and delayed cell death after 24 h. These findings suggest that rapid pressure fluctuations associated with head impact may induce time-dependent mechanobiological responses in endothelial cells, thereby contributing to microvascular damage following traumatic brain injury.
Increasing diameter and blood flow velocity contribute independently to an underestimation of arterial saturations measured by retinal oximetry.
Drachmann J, Bek T
Microvasc Res · 2026 Jul · PMID 42162646 · Publisher ↗
PURPOSE: The oxygen saturation measured by oximetry in retinal arterioles has been shown to be inversely related to both the vessel diameter and the blood flow velocity. The purpose of the present study was to investigat...
PURPOSE: The oxygen saturation measured by oximetry in retinal arterioles has been shown to be inversely related to both the vessel diameter and the blood flow velocity. The purpose of the present study was to investigate whether these parameters contribute independently to the variation in the measured oxygen saturation and whether the measurements are also affected by age, sex, refraction, axial length, heart rate, intraocular pressure, systemic blood pressure and systemic oxygen saturation. METHODS: Retinal oximetry with measurement of vessel diameter, supplemented with Doppler OCT measurements of blood flow velocity, were performed in the four peripapillary branches from the central retinal artery in 28 normal individuals aged 19-38 years. The examinations were repeated during an increase in the arterial blood pressure induced by isometric exercise. RESULTS: The diameter and blood flow velocity contributed independently to the variation in the measured oxygen saturations among the four peripapillary arterioles (p < 0.001 for both variables together, R = 0.20). Age, sex, refraction, axial length, heart rate, mean systemic arterial pressure, intraocular pressure and systemic oxygen saturation showed no significant contribution to the variation in the measured oxygen saturation among individuals. CONCLUSIONS: The accuracy of dual wavelength oximetry measurements of oxygen saturation in retinal vessels can be independently improved by adjusting for the influence of vessel diameter and blood flow velocity.
Impact of various forms of vitamin D on endothelial dysfunction triggered by high glucose conditions in Wistar rats.
Le Jan D, Gourmelon M, Destrumelle S … +2 more , Desfontis JC, Mallem MY
Microvasc Res · 2026 Jul · PMID 42114617 · Publisher ↗
BACKGROUND: Endothelial dysfunction (ED) is a hallmark of metabolic disturbances such as Metabolic Syndrome (MetS), where oxidative stress and reduced nitric oxide (NO) bioavailability play key roles. High glucose (HG),...
BACKGROUND: Endothelial dysfunction (ED) is a hallmark of metabolic disturbances such as Metabolic Syndrome (MetS), where oxidative stress and reduced nitric oxide (NO) bioavailability play key roles. High glucose (HG), a major metabolic alteration in MetS, impairs endothelial signaling in large conduit arteries and microvascular beds through shared mechanisms, including excessive reactive oxygen species (ROS) production and altered endothelial nitric oxide synthase (eNOS) activity. OBJECTIVE: This study investigated HG-induced ED in rat thoracic aorta and examined the effects of different vitamin D forms on vascular reactivity under HG conditions. METHODS: Thoracic aortas from twelve-week-old male Wistar rats were incubated under normal glucose (NG, 11.1 mM) or HG (44.4 mM) conditions for 3 h and treated with tempol (10 M), cholecalciferol (VD1; 10 M), calcidiol (VD2; 10 M), or calcitriol (VD3; 10 M). Endothelium-dependent vasorelaxation was assessed using cumulative concentration-response curves (CCRCs) to acetylcholine (Ach; 10 to 3.10 M); vasoconstriction was evaluated using phenylephrine (Phe; 10 to 3.10 M). RESULTS: HG impaired ACh-mediated vasorelaxation and increased Phe-induced vasoconstriction. Tempol fully restored endothelial function under HG conditions, confirming the predominant role of oxidative stress. Both cholecalciferol and calcitriol improved ACh-mediated vasorelaxation (pD and E) toward NG levels and reduced α-adrenergic hyperresponsiveness, although not significantly. Calcidiol showed no significant effect. CONCLUSION: Cholecalciferol and calcitriol counteract HG-induced endothelial dysfunction in rat aorta, suggesting that specific vitamin D forms modulate endothelial signaling pathways disrupted in metabolic disturbances. These findings support their therapeutic potential in restoring vascular homeostasis in HG conditions.
Noninvasive, in vivo, high-resolution investigation of conjunctival vessels in diabetes and hypertension patients.
Mou D, Zhang J, Zhao Z … +1 more , Chen H
Microvasc Res · 2026 Jul · PMID 42103095 · Publisher ↗
PURPOSE: Vascular changes are key pathological features in many diseases, such as hypertension and diabetes. This study aimed to investigate the morphological changes of bulbar conjunctival vessels in hypertension and di...
PURPOSE: Vascular changes are key pathological features in many diseases, such as hypertension and diabetes. This study aimed to investigate the morphological changes of bulbar conjunctival vessels in hypertension and diabetes using laser scanning confocal microscopy (LSCM). METHODS: Patients with hypertension, diabetes, co-occurrence and age-matched control were recruited. Temporal bulbar conjunctiva 3-5 mm away from limbus was imaged using LSCM. The vessels were classified as arteries or veins. The wall-lumen thickness ratio (WLTR) and wall-lumen reflectivity difference (WLRD) were compared among different groups. Multivariant linear regression was used to assess the predictors of conjunctival parameters. RESULTS: A total of 93 eyes of 93 patients were included. The WLTR of conjunctival arteries in diabetes group (0.66 ± 0.22) and co-occurrence group (0.76 ± 0.41) were higher than in control group (0.48 ± 0.15). The WLRD of conjunctival arteries in co-occurrence group (66.68 ± 25.48) was higher than in control group (45.21 ± 23.40) and hypertension group (51.91 ± 24.75). The WLTR of conjunctival veins in co-occurrence group (0.43 ± 0.21) was higher than in control group (0.28 ± 0.11). No significant difference was found in vein WLRD among the groups. In multiple linear regression, diabetes and hypertension were associated with artery WLTR, vein WLTR and artery WLRD, but no factor was associated with vein WLRD. CONCLUSIONS: LSCM provides in vivo, noninvasive, high-resolution imaging of morphological changes in conjunctival vessels. Both hypertension and diabetes increase the WLTR of conjunctival artery and vein, as well as the WLRD of conjunctival artery but not the vein.
Endothelial cell dysfunction and postoperative complications in patients with severe mesenteric traction syndrome: A prospective cohort study.
Kragbak EJ, Achiam MP, Burgdorf S … +7 more , Goetze JP, Aasvang EK, Siemsen M, Omar GA, Johansson PI, Svendsen MBS, Olsen-Nedergaard AA
Microvasc Res · 2026 Jul · PMID 42055211 · Publisher ↗
BACKGROUND: Mesenteric traction syndrome (MTS) is characterized by tachycardia, hypotension, and facial flushing during abdominal surgery. Previous studies suggest that severe MTS is associated with increased complicatio...
BACKGROUND: Mesenteric traction syndrome (MTS) is characterized by tachycardia, hypotension, and facial flushing during abdominal surgery. Previous studies suggest that severe MTS is associated with increased complications as well as endothelial damage. Whereas MTS was previously diagnosed based on subjective flushing, a recent study has validated an objective measure of facial flushing using laser speckle contrast imaging. However, no studies have yet examined the association between objectively diagnosed severe MTS (qsMTS), endothelial dysfunction, and postoperative complications. METHODS: Patients underwent either open pancreatic surgery or open esophagectomy for non-disseminated cancer. qsMTS was measured using laser speckle contrast imaging. Blood samples for endothelial damage and activation (soluble Thrombomodulin, VEGFR1, and Syndecan-1) were collected at predetermined intervals before and after surgery. RESULTS: In total, 61 patients were included, of whom 19 (31%) had qsMTS. qsMTS was associated with a Comprehensive Complication Index ≥26.2 (p = 0.010). No association was found between qsMTS-status and plasma concentrations of soluble Thrombomodulin, Syndecan-1, or VEGFR1 at any time point (p > 0.13 for all). CONCLUSION: Severe MTS remains a significant risk factor for severe postoperative complications following major abdominal surgery when diagnosed objectively. Although we hypothesized that this association might be partly mediated by increased endothelial damage and activation, our findings do not support this, as no association was observed between circulating endothelial markers and qsMTS or postoperative complications.
From retina to triple-monitoring: One-carbon metabolism in diabetic retinopathy.
Mohamed MSA
Microvasc Res · 2026 Jul · PMID 42049165 · Publisher ↗
BACKGROUND: Diabetic retinopathy (DR) is a microvascular complication of diabetes characterized by blood-retinal barrier (BRB) disruption and progressive endothelial dysfunction. Disturbances in one-carbon metabolism, pa...
BACKGROUND: Diabetic retinopathy (DR) is a microvascular complication of diabetes characterized by blood-retinal barrier (BRB) disruption and progressive endothelial dysfunction. Disturbances in one-carbon metabolism, particularly hyperhomocysteinemia (HHcy), have been implicated as biologically plausible modifiers of retinal endothelial vulnerability. OBJECTIVE: To synthesize mechanistic, preclinical, and clinical evidence linking HHcy and one-carbon metabolism to BRB dysfunction in DR, and to explore translational implications for endothelial risk assessment. METHODS: Narrative review of experimental, observational, and translational studies examining homocysteine metabolism, endothelial regulation, BRB integrity, and diabetes-induced metabolic perturbations. Evidence was prioritized based on mechanistic relevance, in vitro and in vivo models, and human correlates. RESULTS: Elevated homocysteine promotes oxidative stress, tight junction destabilization, N-methyl-d-aspartate receptor activation, mitochondrial dysfunction, and impaired mitophagy in retinal endothelial cells. Diabetes amplifies these pathways, lowering the threshold for VEGF-mediated BRB breakdown. Observational studies associate HHcy with DR severity, but causality remains unproven. Cardiovascular trials demonstrate plasma homocysteine lowering without consistent macrovascular benefit, suggesting HHcy functions primarily as a biomarker or modifier. Emerging data indicate potential intersections with innate immune signaling and ferroptotic vulnerability, offering mechanistic hypotheses for translational research. Integrative frameworks considering glycemic control, one-carbon metabolic status, and endothelial signaling may inform future early-intervention strategies, though clinical validation is pending. CONCLUSIONS: HHcy represents a mechanistic modifier of retinal endothelial stress in DR rather than a validated therapeutic target. Anti-VEGF therapy and glycemic optimization remain the only proven interventions. Further studies clarifying intracellular one-carbon metabolism and BRB integrity may refine risk stratification and identify early-intervention opportunities.
Linagliptin enhances coronary microvascular function and collateralization in a large animal model of cardiometabolic syndrome.
Muir KC, Harris DD, Stone C … +4 more , Kanuparthy M, Hamze J, Feng J, Sellke FW
Microvasc Res · 2026 Jul · PMID 42049164 · Publisher ↗
INTRODUCTION: Metabolic syndrome has been shown to double the risk of cardiovascular-related mortality. Therefore, it deems efficacious not only to treat the underlying systemic metabolic pathways but also aim to improve...
INTRODUCTION: Metabolic syndrome has been shown to double the risk of cardiovascular-related mortality. Therefore, it deems efficacious not only to treat the underlying systemic metabolic pathways but also aim to improve cardiovascular function. Thus, we sought to determine the cardiovascular effects of dipeptidyl peptidase 4 (DPP-4) inhibition with linagliptin in a clinically relevant model of coronary artery disease in the setting of metabolic syndrome. METHODS: To induce metabolic syndrome, Yorkshire swine were fed a high-fat diet for 5 weeks and then underwent ameroid constrictor placement to the left circumflex artery, causing coronary artery disease. Swine were treated with either no drug (n = 8) or daily linagliptin (n = 8). After 5 weeks, swine underwent terminal harvest for hemodynamic characterization and tissue collection. To assess microvascular reactivity, coronary arterioles were dissected and mounted to visualize the in-vitro response to vasorelaxation agents. RESULTS: Linagliptin treatment did not improve overall cardiac function, including ejection fraction and cardiac output (p > 0.05). Linagliptin treatment was associated with upregulation of the glucagon-like peptide-1 receptor, protein kinase A signaling and several other angiogenic markers, and increased collateralization within the ischemic myocardium. Correspondingly, treated swine exhibited enhanced ischemic microvascular vasorelaxation to both endothelial-dependent adenosine diphosphate (ADP) and endothelial-independent sodium nitroprusside (SNP) (p = 0.004, p = 0.024; respectively), accompanied by increased expression of phosphorylated endothelial nitric oxide synthase (eNOS) and the ratio of phospho-to-total eNOS (p = 0.009, p = 0.002; respectively). CONCLUSIONS: Linagliptin represents a promising therapeutic shown to improve collateralization, enhance arteriolar reactivity, and quell endothelial dysfunction in a translational model of metabolic syndrome.
Microvascular and stromal normalization combined with nano-immunotherapy: A synergistic strategy to overcome drug delivery barriers in solid tumors.
Mirala F, Kashkooli FM, Soltani M
Microvasc Res · 2026 Jul · PMID 42019574 · Publisher ↗
Solid tumors like advanced-stage prostate carcinoma pose significant hindrances to therapeutic approaches due to a rich tumor microenvironment (TME) that establishes strong physical and immune resistance to treatment. Th...
Solid tumors like advanced-stage prostate carcinoma pose significant hindrances to therapeutic approaches due to a rich tumor microenvironment (TME) that establishes strong physical and immune resistance to treatment. The TME is defined by a dense, fibrotic stroma and non-functional vasculature, which produce high mechanical stress, high interstitial fluid pressure (IFP), and hypoxia. These properties critically inhibit therapeutic agent penetration and suppress anti-tumor immunity. This review details the mechanistic foundation of such hindrances and discusses the nascent paradigm of TME normalization. This review critically evaluates approaches aimed at stromal normalization, which include anti-cancer stroma cell targeting and extracellular matrix (ECM) degradation, as well as vascular normalization, which involves anti-angiogenic therapy for vessel repair. The unifying hypothesis of this review is that therapeutic efficacy in advanced solid tumors can be significantly enhanced by first restoring key abnormalities of the tumor microenvironment, including vascular dysfunction and stromal stiffness, thereby improving perfusion, reducing hypoxia, and facilitating immune cell and nanoparticle penetration. This microenvironmental normalization creates a transient therapeutic window that can be strategically exploited through nano-immunotherapy. This strategy enhances the penetration of nanoparticles, streamlines immune cell migration, and counteracts immune suppression. Lastly, key clinical issues and future directions include optimal scheduling, predictive markers, and next-generation nanocarriers. This overall strategy offers a combined method to overcome cancer resistance while improving outcomes in difficult-to-treat tumors.
Erectile dysfunction as an early biomarker of cardiovascular toxicity: Mechanisms and clinical implications.
Jaiswal R, Devi N, Chauhan L … +10 more , Ahmad S, Pandey S, Tiwari K, Yadav AK, Ali A, Jaiswal R, Reetu, Khanam A, Yadav R, Ahsan R
Microvasc Res · 2026 Jul · PMID 42009193 · Publisher ↗
Erectile dysfunction (ED) has been traditionally regarded as a quality-of-life disorder; however, accumulating evidence positions it as an early and clinically actionable biomarker of cardiovascular toxicity. ED and card...
Erectile dysfunction (ED) has been traditionally regarded as a quality-of-life disorder; however, accumulating evidence positions it as an early and clinically actionable biomarker of cardiovascular toxicity. ED and cardiovascular disease share fundamental pathophysiological mechanisms including endothelial dysfunction, reduced nitric oxide bioavailability, oxidative stress, systemic inflammation, autonomic imbalance, and vascular smooth muscle dysfunction. Because penile cavernosal arteries (~1-2 mm diameter) are substantially smaller than coronary arteries (~3-4 mm), the penile vascular bed manifests endothelial injury earlier, conferring a sentinel role on ED. Two temporally distinct patterns must be recognized: in men with traditional cardiovascular risk factors, ED precedes overt cardiovascular events by 2-5 years, reflecting shared systemic endothelial pathology; whereas drug-induced ED emerges within months to 2 years of therapy initiation, representing an acute or subacute microvascular adverse effect specific to the causative agent. Several drug classes, including anthracycline-based chemotherapy, androgen deprivation therapy, tyrosine kinase inhibitors, VEGF inhibitors, and immune checkpoint inhibitors, induce both cardiovascular toxicity and ED through overlapping microvascular mechanisms, each with a characteristic onset timeline. A structured five-step clinical framework integrating IIEF-5 screening, cardiovascular risk scoring augmented by NT-proBNP and high-sensitivity troponin, ECG-derived diastolic dysfunction indexing, and multimodality imaging including echocardiography with global longitudinal strain, coronary artery calcium scoring, and carotid intima-media thickness is proposed to operationalise ED-guided cardiovascular monitoring. This review highlights mechanistic links, discusses diagnostic and prognostic relevance, and emphasizes multidisciplinary strategies for mitigating long-term cardiovascular outcomes.
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