Microvascular Research[JOURNAL]
Sun
200 papers
Angiogenic and intraplatelet growth biomarkers in systemic sclerosis.
Flores Robles BJ, Gómez Casado C, Bueno Cabrera JL … +8 more , Núñez Martín-Buitrago L, Mulero Mendoza J, Salazar Asencio OA, Godoy Tundidor H, Rusinovich Lovgach O, Martos Gisbert N, Andréu Sánchez JL, Sánchez López A
Microvasc Res · 2026 Jul · PMID 41985713 · Publisher ↗
BACKGROUND: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy, immune system dysregulation, and fibrosis. There is growing evidence regarding the role of platelets in innate immunity...
BACKGROUND: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy, immune system dysregulation, and fibrosis. There is growing evidence regarding the role of platelets in innate immunity and inflammatory processes, as they are an important source of mediators that may be key factors in the pathogenesis of SSc. Here we study the intraplatelet and plasma levels of various growth factors (GFs) and angiogenic factors in patients with SSc. METHODS: The sample included 23 SSc patients and 16 controls. We determined the subjects' levels of factors (TGF-β, VEGF-A, PDGF-BB, FGF2, G-CSF, HGF, MCP-1), interleukins (IL-1α, IL-1β, IL-6, IL-8, IL-13), serotonin, and histamine in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) samples obtained by apheresis. We quantify the factors using multiplex immunoassays. The results were normalized to plateletcrit. P-values ≤0.05 were considered statistically significant. RESULTS: The intraplatelet levels of the factors analyzed in this study were greater than the plasma levels in both the patients and control groups (P ≤ 0.05). The intergroup comparison (patients vs. controls) revealed that all the factors were at similar levels in PRP and PPP, apart from VEGF-A, which was lower in PRP samples from SSc patients compared to controls (193.10 pg/mL vs. 574.31 pg/mL; P < 0.0001). CONCLUSIONS: We only found significant differences in VEFG-A which was lower in PRP collected from SSc patients compared to controls. We should ask ourselves whether platelets as such lack VEGF-A, making them less effective in angiogenesis and the tissue repair process.
Nailfold videocapillaroscopy reveals early microvascular changes in pediatric epilepsy.
Perk P, Çakmak F, Koç R … +3 more , Dağdelen ZÖ, Yüksel A, Demirkan FG
Microvasc Res · 2026 Jul · PMID 41967572 · Publisher ↗
UNLABELLED: Nailfold videocapillaroscopy (NVC) provides a non-invasive and reproducible approach to visualize and quantify microvascular morphology. Originally standardized for evaluating Raynaud's phenomenon and systemi...
UNLABELLED: Nailfold videocapillaroscopy (NVC) provides a non-invasive and reproducible approach to visualize and quantify microvascular morphology. Originally standardized for evaluating Raynaud's phenomenon and systemic sclerosis, NVC has recently been applied to a broader range of non-rheumatologic conditions. In epilepsy, both the disease process and long-term exposure to anti-seizure medications (ASMs) may alter endothelial function and microvascular integrity. The present study was conducted to examine the relationship between ASM monotherapy and nailfold capillary morphology in children with epilepsy. METHODS: This cross-sectional study included 36 children with epilepsy and 38 age- and sex-matched controls. All patients received monotherapy with valproic acid (VPA), carbamazepine (CBZ), levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), or topiramate (TPM) for ≥6 months. NVC (×200 magnification) was used to assess capillary density, apical loop diameter, tortuosity, hemorrhages, and abnormal morphology. RESULTS: Compared with controls, patients exhibited significantly wider apical loop width (15.6 [13.1-17.4] μm vs. 14 [13-15] μm; p = 0.007) and a higher frequency of reduced capillary density (<7 cap/mm: 25% vs. 5.3%; p = 0.023). Dilated capillaries were also more frequent among patients (41.7% vs. 15.8%; p = 0.020). Correlation analysis demonstrated positive associations between treatment duration and apical loop width (r = 0.32, p = 0.055), dilated capillary count (r = 0.36, p = 0.043), and abnormal capillary count (r = 0.40, p = 0.025). In subgroup analyses, patients treated with VPA and CBZ had significantly lower capillary density than those receiving newer-generation ASMs (p = 0.023). In contrast, crossed capillaries were more prominent in the newer-drug group (p = 0.012). CONCLUSION: Chronic ASMs exposure, particularly valproic acid, may lead to subtle but measurable alterations in microcirculation. NVC may serve as a practical, non-invasive method for the early detection of endothelial dysfunction in pediatric epilepsy and could aid long-term vascular monitoring in this population.
A comparative analysis of CFD and LBM for investigating the effects of endothelial glycocalyx on the bifurcating blood flow.
Zhou H, Xing J, Sun Q … +4 more , Liu Y, Sun M, Goligorsky MS, Jiang XZ
Microvasc Res · 2026 Jul · PMID 41951140 · Publisher ↗
The surface of vascular endothelial cells is covered by endothelial glycocalyx. The fragile, hair-like structure of endothelial glycocalyx makes difficult to gauge its interactions with circulating blood flow and cells i...
The surface of vascular endothelial cells is covered by endothelial glycocalyx. The fragile, hair-like structure of endothelial glycocalyx makes difficult to gauge its interactions with circulating blood flow and cells in experimental settings. Numerical simulations, capable of mimicking intact or damaged glycocalyx conditions, have emerged as an effective tool to understand the interplay between the endothelial glycocalyx and blood flow, although results may vary due to algorithmic differences. In the present study, classical CFD (computational fluid dynamics) and LBM (lattice Boltzmann method) were used to mimic the interactions between the endothelial glycocalyx and blood flow. The effects of endothelial glycocalyx intactness on blood flow velocity and shear stress were investigated under physiologically relevant conditions. The effects of vessel geometry on red blood cell movement and the effects of glycocalyx intactness were further studied in the CFD simulations. The results suggested that the flow velocities in the downstream branches, which are determined by the blood vessel diameters, affected the movement of red blood cells in the upstream feeding-channel significantly. The findings agree with the Zweifach-Fung effect reported previously. Additionally, the flow profiles and computational execution details of the CFD and LBM were compared. Notably, LBM can capture fine details of the flow and exhibits higher computational efficiency, approximately 15 times that of the CFD method. The findings will clarify the behavior of the blood flow over the complicated vessel surface and provide insights for the selection of optimal numerical methods in solving blood flow problems on topographically complex surfaces.
Integrating microcirculatory imaging, optical oxygenation indices, and cellular redox state to assess tissue vitality.
Aksu U
Microvasc Res · 2026 Jul · PMID 41942062 · Publisher ↗
Although modern resuscitation strategies increasingly incorporate parameters such as lactate kinetics and venous oxygenation, clinical practice still predominantly relies on macrocirculatory targets. However, restoring s...
Although modern resuscitation strategies increasingly incorporate parameters such as lactate kinetics and venous oxygenation, clinical practice still predominantly relies on macrocirculatory targets. However, restoring systemic hemodynamics often fails to correct cellular dysoxia due to a loss of hemodynamic coherence. This perspective proposes an integrated framework that assesses tissue vitality by combining microcirculatory imaging, optical oxygenation indices, and mitochondrial redox state. By simultaneously evaluating convective flow, oxygen availability, and metabolic utilization, this multi-domain approach can reveal organ dysfunction and guide resuscitation toward genuine cellular recovery rather than macro-circulatory targets alone.
Assessing the retinal microvasculature in heart failure: A systematic review and possible clinical implications.
Vanreusel I, Van Eijgen J, Jena F … +10 more , Vermeulen D, Gevaert AB, Van Craenenbroeck AH, Cornelissen V, Van Aelst LNL, Van Edom C, Van Berendoncks A, Segers VFM, Stalmans I, Van Craenenbroeck EM
Microvasc Res · 2026 Jul · PMID 41916510 · Publisher ↗
BACKGROUND: Despite an extensive armamentarium, the long-term prognosis of heart failure remains poor, and its pathophysiology is still not fully understood. Microvascular function is impaired early in the development of...
BACKGROUND: Despite an extensive armamentarium, the long-term prognosis of heart failure remains poor, and its pathophysiology is still not fully understood. Microvascular function is impaired early in the development of HF and linked to disease progression. Retinal imaging provides a unique opportunity for fast, non-invasive and affordable detection of early systemic microvascular disease. AIM: To provide a systematic overview of current literature regarding retinal microvascular changes in HF. METHODS: A literature search was performed using MEDLINE, EMBASE, Web of Science and Cochrane Library (Registration number: INPLASY202450114). Studies on retinal microvascular changes, visualized by fundus photography, adaptive optics, optical coherence tomography, scanning laser Doppler flowmetry and dynamic vessel analysis in patients with HF were included. RESULTS: Twenty-four articles were included for qualitative analysis. Compared to healthy controls, patients with HF consistently exhibited reduced flicker light-induced dilation of retinal arterioles and venules, as well as decreased vessel density around the optic nerve head. More limited evidence suggests an increase in arteriolar wall thickness and wall cross-sectional area. Findings supporting other structural changes in the retinal microvessels were inconsistent. The pathophysiology behind retinal vascular abnormalities in HF and their correlation with HF severity remain incompletely understood. Nevertheless, retinal imaging holds promise for identifying individuals at risk of developing HF and predicting prognosis. Overall, analysis of retinal microvascular structure and function could serve as a valid surrogate marker for future interventional studies in HF. CONCLUSION: This review provides a systematic overview on retinal imaging as a promising tool in the prevention, risk stratification and management of HF, and as a surrogate marker in clinical trials.
Docosahexaenoic and eicosapentaenoic acids differentially enhance the blood-brain barrier function via distinct PPAR-dependent upregulation of tight junction proteins in brain endothelial cells.
Iwao T, Takata F, Tanaka Y … +3 more , Aridome H, Mizoguchi J, Dohgu S
Microvasc Res · 2026 Jul · PMID 41895681 · Publisher ↗
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are unsaturated omega-3 fatty acids that reduce the risk of Alzheimer's disease and dementia by protecting blood-brain barrier (BBB) function. However, the mecha...
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are unsaturated omega-3 fatty acids that reduce the risk of Alzheimer's disease and dementia by protecting blood-brain barrier (BBB) function. However, the mechanisms through which DHA and EPA regulate BBB function remain unclear. DHA and EPA act as ligands for the peroxisome proliferator-activated receptor (PPAR), which is a nuclear receptor superfamily member, with three isoforms: α, β, and γ. Tight junctions (TJs) formed between brain endothelial cells play a central role in restricting the paracellular passage of substances across the BBB. In this study, we aimed to investigate whether DHA and EPA regulate TJ protein expression via PPARs. Primary cultured rat brain endothelial cells (RBECs) isolated from Wistar rats were used for in vitro analysis. TJ protein (ZO-1, occludin, and claudin5) and PPARα, β, and γ expression levels in RBECs were measured using western blot analysis. Additionally, to verify PPAR involvement in TJ protein expression regulation, RBECs were treated with DHA or EPA in combination with PPARα, β, or γ inhibitors. The DHA-induced ZO-1 upregulation was suppressed by PPARβ inhibition. Either PPARβ or PPARγ inhibition suppressed the DHA-induced occludin increase, whereas both PPAR inhibitors suppressed the DHA-induced claudin-5 increase. In contrast, the EPA-induced increase in claudin-5 expression was suppressed via PPARγ inhibition. Conclusively, DHA and EPA regulate TJ protein expression via different PPARs in brain endothelial cells, revealing potential targets for the prevention or treatment of neurodegenerative diseases.
Retinal imaging and AI for non-invasive detection of diabetic macrovascular complications.
Ezhil GR, Sridevi S
Microvasc Res · 2026 Jul · PMID 41895680 · Publisher ↗
BACKGROUND: Diabetes mellitus accelerates vascular degeneration and increases the risk of major macrovascular complications, including Peripheral Arterial Disease (PAD) and aortic pathologies, collectively termed Periphe...
BACKGROUND: Diabetes mellitus accelerates vascular degeneration and increases the risk of major macrovascular complications, including Peripheral Arterial Disease (PAD) and aortic pathologies, collectively termed Peripheral Arterial and Aortic Diseases (PAAD). These conditions are strongly associated with adverse cardiovascular outcomes but often remain underdiagnosed in diabetic populations due to asymptomatic progression and limited access to early screening. OBJECTIVE: This study aims to develop and validate a non-invasive, artificial intelligence (AI)-based screening framework using retinal fundus imaging for early detection of PAAD by exploiting retinal microvascular features as systemic biomarkers. METHODS: A hybrid diagnostic pipeline integrated simulated Optical Coherence Tomography (OCT)-like structural features (retinal thickness, texture entropy, vessel density factor, and layer separation index), handcrafted vascular biomarkers, and an attention-enhanced VGG16 backbone with Convolutional Block Attention Modules (VGG16 + CBAM). Multiple Instance Learning (MIL) improved lesion-level discrimination in weakly labeled datasets. Multi-level feature fusion aggregated spatial, physiological, and morphological descriptors. High-resolution fundus datasets from public and clinical cohorts were used for training and validation. Model interpretability was ensured using SHapley Additive exPlanations (SHAP) and Gradient-weighted Class Activation Mapping (Grad-CAM). RESULTS: The framework achieved an accuracy of 94.6%, sensitivity of 90.5%, specificity of 96.2%, and an AUC-ROC of 0.973 on an independent test set. SHAP identified retinal thickness and texture entropy as dominant predictors, while Grad-CAM highlighted vessel bifurcations and arteriolar narrowing, consistent with PAAD pathophysiology. The average inference time was 150 ms per image on GPU, enabling real-time use. CONCLUSION: This interpretable AI-based system demonstrates high diagnostic performance for PAAD detection using retinal imaging. It offers a non-invasive, cost-effective, and scalable alternative to conventional vascular assessments and may support earlier diagnosis and improved prevention of cardiovascular and cerebrovascular complications.
PEAR1/EAF1 deficiency impairs aspirin responsiveness in atherosclerotic endothelium: A novel mechanism of atypical aspirin resistance.
Liu J, Peng J, Zhan Y … +3 more , Liu L, Xu K, Xie Y
Microvasc Res · 2026 Jul · PMID 41881247 · Publisher ↗
BACKGROUND: Aspirin resistance (AR) severely limits the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Traditionally, aspirin resistance is attributed to intrinsic defects in blood cells, such as...
BACKGROUND: Aspirin resistance (AR) severely limits the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Traditionally, aspirin resistance is attributed to intrinsic defects in blood cells, such as platelets or erythrocytes. However, the failure of aspirin to suppress endothelial inflammation, a key driver of residual cardiovascular risk, remains overlooked. We hypothesize that AR is partly an endothelial pathology mediated by the Platelet Endothelial Aggregation Receptor 1 (PEAR1) / ELL-associated factor 1 (EAF1) interaction. METHODS: We integrated bioinformatic analyses, including weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, and support vector machine-recursive feature elimination (SVM-RFE), using bulk RNA sequencing (RNA-seq) data (GSE38511) and single-cell RNA sequencing (scRNA-seq) data (GSE159677) to identify and localize AR-related hub genes. An in vitro AR-like endothelial model was established in human umbilical vein endothelial cells (HUVECs) using oxidized low-density lipoprotein (ox-LDL), tumor necrosis factor-alpha (TNF-α), and aspirin. Key inflammatory and signaling changes were further validated in human aortic endothelial cells (HAECs). The effects of PEAR1 and EAF1 overexpression on endothelial function and the nuclear factor kappa B (NF-κB) / NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway were assessed by Western blotting, quantitative real-time polymerase chain reaction (qPCR), immunofluorescence, and functional assays. RESULTS: Bioinformatics identified PEAR1 and EAF1 as core hub genes significantly associated with AR and primarily localized to endothelial cells (ECs). In the in vitro AR model, PEAR1 and EAF1 expression was significantly decreased, which correlated with activation of the NF-κB/NLRP3 pathway. Similar inflammatory and signaling changes were confirmed in HAECs, supporting the reproducibility of the endothelial hyporesponsive phenotype in an alternative arterial endothelial model. Conversely, co-overexpression of PEAR1 and EAF1 synergistically suppressed phosphorylation of NF-κB p65 and expression of NLRP3. This interaction also inhibited endothelial migration and invasion while promoting apoptosis. CONCLUSION: The PEAR1/EAF1 interaction ameliorates aspirin resistance in atherosclerosis. This effect is associated with suppression of the endothelial NF-κB/NLRP3 inflammatory signaling pathway and altered endothelial cell fate under inflammatory stress. Targeting the PEAR1/EAF1 interaction represents a novel potential therapeutic strategy for overcoming AR.
Targeting of the PI3K/AKT/mTOR signaling pathway in the neurovascular interface in both Alzheimer's disease and atherosclerosis: The potential nexus.
Alameen AAM, Al-Kuraishy HM, Al-Gareeb AI … +2 more , Shokr MM, Batiha GE
Microvasc Res · 2026 Jul · PMID 41865874 · Publisher ↗
Alzheimer's disease (AD) and atherosclerosis (AS) are traditionally viewed as distinct neurodegenerative and vascular disorder respectively. However, emerging evidence reveals a profound molecular cross-talk and pathophy...
Alzheimer's disease (AD) and atherosclerosis (AS) are traditionally viewed as distinct neurodegenerative and vascular disorder respectively. However, emerging evidence reveals a profound molecular cross-talk and pathophysiological interplay between these two conditions. This review explores the molecular crossroads where AD and AS converge, identifying shared signaling pathways that offer novel therapeutic opportunities. At the center of this connection is amyloid-beta (Aβ), which serves as a systemic molecular nexus. While central Aβ accumulation is a hallmark of AD, peripheral Aβ, produced in tissues such as skeletal muscle and pancreas, can cross the blood-brain barrier (BBB) to induce endothelial dysfunction and neurovascular inflammation. This review highlights how common molecular hubs, including the PI3K/AKT/GSK3β, mTOR, PP2A, and PTEN signaling pathways, drive the pathogenesis of both diseases by regulating oxidative stress, inflammation, and autophagy. By addressing these shared mechanisms, the review proposes a paradigm shift toward dual-purpose therapies. Modulating Aβ clearance, inhibiting the over-activated GSK3β, or utilizing mTOR inhibitors and PP2A activators could concurrently mitigate neurodegeneration and stabilize atherosclerotic plaques. Ultimately, recognizing AD and AS as interconnected systemic disorders provides a compelling rationale for multidisciplinary clinical strategies and integrated pharmacological interventions to improve outcomes in an aging population.
Tumour angiogenesis and ferroptosis: A metabolic oxidative stress-driven aberrant vascularisation and therapeutic vulnerabilities.
Mukherjee B, Vidhate D, Rao R … +3 more , Deb P, Deb A, Vidhate A
Microvasc Res · 2026 Jul · PMID 41833600 · Publisher ↗
Tumour angiogenesis, a hallmark of cancer progression, involves the formation of new vasculature to sustain malignant growth. It is driven by complex molecular signalling networks responsive to hypoxia, inflammation, and...
Tumour angiogenesis, a hallmark of cancer progression, involves the formation of new vasculature to sustain malignant growth. It is driven by complex molecular signalling networks responsive to hypoxia, inflammation, and metabolic stress. This article is an attempt to analyse and integrate recent insights into the molecular mechanisms underlying angiogenesis, its diagnostic and therapeutic implications, and its emerging intersection with ferroptosis - an iron-dependent, regulated form of cell death. Key pathways such as VEGF, PDGF, IGF, TGF-β and their downstream effectors such as PI3K/Akt, MAPK, ERK, etc., as well as molecular regulators linking oxidative stress and lipid peroxidation to angiogenic responses, are crucial in framing the tumour microenvironment. Understanding these pathways provides a foundation for developing novel combinatorial strategies targeting both angiogenesis and ferroptosis for improved cancer therapy.
Association between systemic microvascular dysfunction and resistant hypertension: Insights from a clinical observational study.
Crahim V, Verri V, De Lorenzo A … +2 more , Kasal D, Tibirica E
Microvasc Res · 2026 Jul · PMID 41833599 · Publisher ↗
BACKGROUND: Resistant arterial hypertension (RAH) is defined as failure to achieve adequate blood pressure control despite the use of at least three antihypertensive drug classes at maximally tolerated doses, including a...
BACKGROUND: Resistant arterial hypertension (RAH) is defined as failure to achieve adequate blood pressure control despite the use of at least three antihypertensive drug classes at maximally tolerated doses, including a diuretic. This phenotype confers markedly elevated cardiovascular risk. Systemic microvascular dysfunction is believed to contribute significantly to its pathophysiology. In non-resistant arterial hypertension (NRAH), early endothelial impairment and increased vasomotor tone are present but may remain partially reversible. However, direct comparisons of microvascular function across RAH, NRAH, and normotensive individuals are limited. OBJECTIVE: To compare systemic microvascular function among patients with RAH, patients with NRAH, and normotensive controls using laser speckle contrast imaging. METHODS: Microvascular reactivity was assessed at baseline and during acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, as well as post-occlusive reactive hyperemia (PORH). Baseline microvascular conductance, areas under the curve (AUCs) for ACh and SNP, and PORH peak and delta responses were compared using one-way ANOVA. RESULTS: Baseline microvascular conductance was significantly higher in controls than in both hypertensive groups. Endothelium-dependent vasodilation (ACh AUC) showed progressive impairment from controls to NRAH to RAH. PORH responses demonstrated reduced peak microvascular conductance and smaller delta values in RAH compared with NRAH and controls. Endothelium-independent vasodilation (SNP AUC) was also diminished in RAH, suggesting structural arteriolar disorder. CONCLUSION: RAH is associated with marked systemic microvascular impairment affecting both endothelial function and microvascular structure. These alterations occur alongside adverse metabolic and renal disorders, underscoring the complex interplay of vascular, metabolic, and renal mechanisms in treatment-resistant hypertension.
Distinct gene expression profiles in blood-brain barrier capillary endothelial cells between mice and humans.
Miao Y, Wang J, Li W … +4 more , Mäe MA, Jeansson M, Muhl L, He L
Microvasc Res · 2026 Jul · PMID 41831605 · Publisher ↗
OBJECTIVE: Endothelial cells (ECs) are key structural and functional components of the blood-brain barrier (BBB). Mouse models are frequently used to study EC biology within the BBB, yet the extent to which human and mou...
OBJECTIVE: Endothelial cells (ECs) are key structural and functional components of the blood-brain barrier (BBB). Mouse models are frequently used to study EC biology within the BBB, yet the extent to which human and mouse BBB ECs share conserved transcriptomic features remains unclear. Here, we systematically compare transcriptomic profiles of BBB capillary ECs from adult mice and humans. METHODS: We analyzed single-cell and single-nucleus RNA-sequencing datasets from adult mouse and human BBB capillary ECs. Candidate species-specific genes were further validated using two whole brain vasculature datasets, along with data from Allen Brain Atlas and Human Protein Atlas. RESULTS: Despite substantial overall conservation between species, 169 genes were consistently enriched in human BBB capillary ECs compared to mouse, whereas 386 genes were enriched in mouse BBB capillary ECs compared to human. Several genes, including A2M, RUNDC3B, BTNL9 and SPOCK3 exhibited predominant expression in human BBB capillary ECs, with minimal or undetected expression in mouse. Conversely, Tspan13, Pglyrp1, Ucp2 and Slco1c1 were specifically expressed in mouse BBB capillary ECs compared with human. Notably, a considerable proportion of differentially expressed genes belonged to the solute carrier (SLC) transporter family. CONCLUSIONS: Our cross-species in-depth analysis reveals both broad conservation and distinct transcriptomic differences between human and mouse BBB capillary ECs. Together, our findings provide a valuable framework for interpreting mouse BBB data in a translational context and for guiding future studies of endothelial biology in the human brain.
Endothelial dysfunction is a risk factor for lipid metabolism disorders: underlying mechanisms and potential treatments.
Liu J, Li L, Lin W … +4 more , Guo W, Sun J, Liu Z, He F
Microvasc Res · 2026 Jul · PMID 41831604 · Publisher ↗
Lipid homeostasis and vascular endothelial function are fundamental to cardiovascular health. This review systematically outlines the regulatory mechanisms that maintain the dynamic balance between the endothelium and sy...
Lipid homeostasis and vascular endothelial function are fundamental to cardiovascular health. This review systematically outlines the regulatory mechanisms that maintain the dynamic balance between the endothelium and systemic lipid metabolism, emphasizing the endothelium as an active regulator. The endothelium influences lipid metabolism in multiple organs by regulating vascular tone, angiogenesis, barrier integrity, and inflammatory response. Studies have demonstrated that genetic ablation of endothelial-specific genes disrupts lipid metabolism in key metabolic organs, including the liver, adipose tissue, and skeletal muscle. This impairment of endothelial function may result in obesity, insulin resistance, hyperlipidemia, and MASLD/MASH. The specific mechanisms linking endothelial dysfunction to systemic lipid metabolism are highlighted. This review clarifies the progression of systemic lipid metabolism disorders driven by an imbalance in the "endothelial-lipid metabolism homeostasis axis". Potential therapeutic strategies targeting this axis for lipid-metabolism disorders and related cardiovascular diseases are also discussed.
Knockdown of FGL2 ameliorates retinal microvascular endothelial cell injury and oxidative stress in diabetic retinopathy.
Yang H, Cheng C, Hui P … +3 more , Liu S, Tian G, Zhang X
Microvasc Res · 2026 Jul · PMID 41794280 · Publisher ↗
OBJECTIVE(S): Diabetic retinopathy (DR), a severe microvascular complication of diabetes mellitus (DM), is recognized worldwide as the leading cause of visual impairment and blindness. FGL2 has been linked to microvascul...
OBJECTIVE(S): Diabetic retinopathy (DR), a severe microvascular complication of diabetes mellitus (DM), is recognized worldwide as the leading cause of visual impairment and blindness. FGL2 has been linked to microvascular endothelial cell injury and oxidative stress. This research aims to evaluate the role of FGL2 in influencing retinal microvascular endothelial cell injury and oxidative stress. MATERIALS AND METHODS: Our study established a streptozotocin (STZ, 65 mg/kg)-induced diabetic rat model and cultured human retinal microvascular endothelial cells (HRMECs) under high glucose (HG, 30 mM) conditions. H&E staining and Evans blue leakage assay were performed to evaluate the pathological change and the vascular leakage in DR rats. Subsequently, we assessed the influence of FGL2 knockdown on endothelial barrier function, oxidative stress and the AKT/FOXO1/PLVAP pathway in vitro. RESULTS: FGL2 expression was upregulated in the retinal tissues of DR rats and HG-stimulated HRMECs. In HG-induced HRMEC monolayers, FGL2 knockdown inhibited FITC-dextran flux and increased transendothelial electrical resistance (TEER). Results of immunofluorescence staining of tight junction proteins reveal a decreased number of tight junction discontinuities in FGL2 knockdown-treated HRMEC cells compared to HG-treated HRMEC cells. Silencing of FGL2 decreased ROS production and MDA content, and elevated SOD and CAT activity in HG-treated HRMECs. Mechanistically, FGL2 silencing enhanced the phosphorylation of AKT and FOXO1. Notably, dual-luciferase reporter assay and ChIP-qPCR were conducted to confirm the occupancy of FOXO1 at the PLVAP promoter. Crucially, the protective effects of FGL2 knockdown on barrier function and oxidative stress were effectively reversed by PLVAP overexpression. CONCLUSION: Collectively, our research indicates that FGL2 knockdown can alleviate the impaired barrier function and oxidative stress in retinal microvascular endothelial cells induced by HG, through the AKT-FOXO1-PLVAP pathway.
Integrated experimental and theoretical approaches to microvascular transport and regulation.
Balogh P, Harraz O
Microvasc Res · 2026 Jul · PMID 41794279 · Publisher ↗
The microcirculation is in a continuous state of change as we grow and evolve in both health and disease. The transport characteristics of blood flow through the microcirculation, intercellular signaling in response to l...
The microcirculation is in a continuous state of change as we grow and evolve in both health and disease. The transport characteristics of blood flow through the microcirculation, intercellular signaling in response to local demands, and coordination between these two players strongly influence the adaptation of the microcirculation to support microvascular function. Notably, both biophysical and electrophysiological phenomena contribute to processes which influence new blood vessel growth and adaption, local regulation of vascular tone and control of microvascular blood distribution, or pathologies related to tumor growth or organ dysfunction. High resolution computational models and experimental studies promise to provide new insights into the mechanisms underlying such processes. This special issue focuses on i) computational models which elucidate hemodynamic characteristics unique to the microcirculation, ii) elucidating microvascular signaling related to blood flow regulation and distribution, and iii) integrating hemodynamics and intercellular signaling to identify synergistic roles and mechanistic contributions.
Rivastigmine attenuates LPS-induced cardiotoxicity via modulation of ER stress, oxidative pathways and apoptosis: Evidence from a rat model.
Sarman E, Asci H, Uysal D … +4 more , Selcuk E, Kucuktepe Z, Kolay O, Gulal A
Microvasc Res · 2026 May · PMID 41794278 · Publisher ↗
INTRODUCTION: This study aimed to investigate the potential protective effects of Rivastigmine (RIV) against lipopolysaccharide (LPS)-induced myocardial injury in rats, with a focus on inflammatory, endoplasmic reticulum...
INTRODUCTION: This study aimed to investigate the potential protective effects of Rivastigmine (RIV) against lipopolysaccharide (LPS)-induced myocardial injury in rats, with a focus on inflammatory, endoplasmic reticulum (ER) stress, apoptotic, oxidative stress, and autophagy-related molecular markers. MATERIAL AND METHODS: Thirty-two female Wistar albino rats were randomly assigned to four: (I) Control, (II) LPS, (III) LPS + RIV and (IV) RIV alone. Rats received 0.5-1 mL RIV and LPS 5 mg/kg intraperitoneally. After 24 h, the cardiac tissues were collected for histopathological evaluation. Immunohistochemical staining was performed for nuclear factor kappa B (NF-κB) p65, caspase-3 (Cas-3), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF). Gene expression analysis was also performed for endoplasmic reticulum chaperone BiP (GRP78), bcl-2-associated X (BAX), b-cell lymphoma-2 (BCL2), nuclear factor, erythroid 2-like 2 (NRF2), beclin 1 (BECLIN1), hypoxia-inducible factor-1α (HIF-1α) and sirtuin 1 (SIRT1). RESULTS: LPS administration resulted in significant myocardial damage, characterized by increased expression of GRP78, BAX, HIF-1α, NF-κB, and IL-6, and decreased expression of BCL2, NRF2, and SIRT1. Histopathological findings included cardiomyocyte degeneration, edema, and inflammatory infiltration. RIV treatment markedly attenuated these alterations, suppressed pro-inflammatory and apoptotic markers, and activated NRF2/SIRT1 and BECLIN1-mediated autophagy. CONCLUSION: RIV significantly reduced cardiomyocyte degeneration and improved histological scores compared to LPS-only rats (p < 0.01). Reverse transcription-polymerase chain reaction showed significant downregulation of GRP78, BAX, and HIF-1α, while SIRT1, BCL2 and NRF2 expressions were markedly upregulated (all p < 0.05). Immunohistochemical staining revealed lower IL-6 and Cas-3 scores in the treatment group. These findings highlight RIV's potential as a cardioprotective agent in inflammatory conditions.
Influence of intravascular albumin on the capillary leakage of fluid in humans.
Hahn RG
Microvasc Res · 2026 May · PMID 41785964 · Publisher ↗
BACKGROUND: The Starling equation gives intravascular albumin a unique role in controlling capillary filtration and urine flow. The present study evaluated the strength by which this role is executed, in addition to othe...
BACKGROUND: The Starling equation gives intravascular albumin a unique role in controlling capillary filtration and urine flow. The present study evaluated the strength by which this role is executed, in addition to other factors that statistically influence the capillary leakage and urine flow rates. METHODS: The capillary filtration and the urine flow were estimated by volume kinetic analysis at 2992 time points during 158 intravenous infusion experiments in volunteers and surgical patients who received 25 mL/kg of Ringer solution or 3 mL/kg of 20% albumin. Stepwise multiple regression was used to compare these estimates to a set of perioperative variables. RESULTS: The infusions of Ringer diluted plasma albumin by 5 g/L while 20% albumin increased the same concentration by 6 g/L, and this difference had a profound influence on the studied variables. Despite similar plasma volume expansion (13 versus 11%), the capillary filtration was 10 times higher during the Ringer experiments than during the albumin experiments, and the urine flow was twice as high. Bleeding reduced both flow variables, whereas ongoing surgery accelerated the filtration, but inflammation decreased it, and a high arterial pressure increased the urine flow. Regression analysis predicted 80% of the capillary filtration but only 21% of the urine flow. CONCLUSION: Marked changes in the capillary leakage rate occur when diluting or deliberately increasing the plasma albumin concentration. Similar effects apply to the urine flow, but this rate is governed by a more complex set of variables.
Retinal structural and vascular alterations in diabetic kidney disease: A bidirectional Mendelian randomization study.
Man S, Mou K, Zhang Y … +4 more , Gao Y, Wu X, Xu H, Zhang M
Microvasc Res · 2026 Jul · PMID 41785963 · Publisher ↗
PURPOSE: Growing evidence indicates retinal thickness and microvascular changes have been associated with diabetic kidney disease (DKD). Nevertheless, the causal links between them have yet to be fully elucidated. We uti...
PURPOSE: Growing evidence indicates retinal thickness and microvascular changes have been associated with diabetic kidney disease (DKD). Nevertheless, the causal links between them have yet to be fully elucidated. We utilized Mendelian randomization (MR) to investigate the bidirectional causal relationship between DKD and retinal structural and vascular alterations. METHODS: The bidirectional two-sample MR was conducted using genome-wide association studies (GWAS) summary statistics from European populations. Eight DKD-related phenotypes were investigated in relation to retinal layer thickness and microvascular traits. RESULTS: The forward MR revealed that macroalbuminuria was associated with increased inner nuclear layer (INL) thickness (OR 1.006 [95% CI 1.000-1.012], P = 0.040), and the combined phenotype of chronic kidney disease and diabetic kidney disease (CKD-DN) was linked to greater choroidal thickness (OR 1.005 [95% CI 1.000-1.009], P = 0.047). All DKD showed negative associations with retinal vascular density (RVD) (OR 0.979 [95% CI 0.965-0.993], P = 0.003) and retinal vascular fractal dimension (RVFD) (OR 0.980 [95% CI 0.966-0.993], P = 0.004). In reverse MR, increased INL thickness predicted higher risk of end-stage renal disease (ESRD) (OR 1.444 [95% CI 1.110-1.878], P = 0.006) and extreme chronic kidney disease (CKD) (OR 1.322 [95% CI 1.026-1.704], P = 0.031). Thickening of outer retinal layers was associated with CKD (OR 1.144 [95% CI 1.020-1.284], P = 0.021). CONCLUSIONS: These findings highlight a potential bidirectional causal link between renal dysfunction and retinal neurovascular changes. Retinal imaging biomarkers may serve as noninvasive indicators of DKD risk and progression, warranting further validation.
Longitudinal assessment of endothelial glycocalyx in ST-elevation myocardial infarction: Interplay with oxidative stress and inflammation.
Miranda CH
Microvasc Res · 2026 May · PMID 41785962 · Publisher ↗
BACKGROUND: Microvascular dysfunction (MVD) after ST-elevation myocardial infarction (STEMI) is common and contributes to adverse left ventricular remodeling and reduced survival. Endothelial glycocalyx (eGC) shedding du...
BACKGROUND: Microvascular dysfunction (MVD) after ST-elevation myocardial infarction (STEMI) is common and contributes to adverse left ventricular remodeling and reduced survival. Endothelial glycocalyx (eGC) shedding during STEMI has been proposed as a potential mechanism for MVD. This study evaluated eGC shedding during STEMI, its recovery over time, and its correlations with oxidative stress, inflammation, and endothelial injury. METHODS: In this before-after clinical study, STEMI patients were assessed in the acute phase and again six months later. Circulating biomarkers of eGC shedding (syndecan-1 [SDC-1], hyaluronan [HYAL], sulfated glycosaminoglycans [GAGs]); endothelial injury (thrombomodulin [TBML], tissue plasminogen activator [tPA], vascular endothelial growth factor [VEGF], nitrite); oxidative stress (malondialdehyde [MDA], total hydroperoxides [H₂O₂], superoxide dismutase [SOD], reduced glutathione [GSH], total antioxidant capacity [TAC]); and inflammatory mediators (IL-6, TNF-α) were quantified. Sublingual microcirculation was evaluated using GlycoCheck to estimate the perfused boundary region (PBR), an inverse parameter of eGC thickness. RESULTS: Twenty patients were included, with a mean interval of 188 ± 31 days between assessments. PBR and flow-adjusted PBR decreased significantly from the acute phase to follow-up, indicating eGC restoration. Acute elevations in SDC-1, HYAL, GAGs, MDA, H₂O₂, SOD, tPA, and nitrite were attenuated at six months. Biomarkers of eGC shedding and PBR values correlated positively with indices of oxidative stress, endothelial injury and inflammation. CONCLUSION: eGC shedding occurs during STEMI and shows evidence of recovery in the subsequent months. Correlations between eGC shedding and oxidative stress, endothelial injury and inflammation support a mechanistic interplay contributing to MVD development after STEMI.
Formononetin, an active component of RAS-RH, ameliorates radiation-induced mitochondrial fission dysfunction in endothelial cells via TCs-ECs crosstalk.
Liu A, Lu W, Jiang H … +7 more , Li L, Guo Z, Liu J, Lu G, Yuan J, Zhao X, Li Y
Microvasc Res · 2026 May · PMID 41740669 · Publisher ↗
OBJECTIVE: This study aimed to investigate the mechanisms by which the ultrafiltrate of Radix Angelicae Sinensis and Hedysari (RAS-RH) and its active component formononetin alleviate X-ray radiation-induced injury in rat...
OBJECTIVE: This study aimed to investigate the mechanisms by which the ultrafiltrate of Radix Angelicae Sinensis and Hedysari (RAS-RH) and its active component formononetin alleviate X-ray radiation-induced injury in rat cardiac microvascular endothelial cells (CMECs) through modulation of cardiac telocytes (TCs)-mediated paracrine signaling. METHODS: An in vitro radiation-induced CMEC injury model was established. Mitochondrial function, proliferation, migration, angiogenesis, and apoptosis were assessed using transmission electron microscopy, flow cytometry, mitochondrial probes, 5-ethynyl-2'-deoxyuridine staining, wound-healing and tube-formation assays, Western blotting, and immunofluorescence. Single-cell RNA sequencing, network pharmacology, molecular docking, and molecular dynamics simulations were used to identify formononetin as the key active component of RAS-RH and to predict its regulatory targets. Reverse transcription quantitative real-time polymerase chain reaction and in situ hybridization further validated the underlying mechanisms. RESULTS: X-ray radiation decreased the mitochondrial membrane potential, increased reactive oxygen species levels, and upregulated the expression of mitochondrial fission-related proteins: mitochondrial fission 1 protein (Fis1), dynamin-related protein 1,and mitochondrial fission factor, thereby inducing mitochondrial dysfunction. These changes suppressed endothelial cells (ECs) proliferation, migration and tube formation and downregulated the expression of endothelial growth factors, such as vascular endothelial growth factor, basic fibroblast growth factor, and angiopoietin-2. In contrast, formononetin, as the active component of RAS-RH upregulated androgen receptor (AR) transcription in TCs and enhanced the expression and paracrine release of TCs-derived miR-151a-5p, which subsequently downregulated Fis1 expression in ECs and inhibited Fis1-mediated excessive mitochondrial fission. Through these mechanisms, formononetin attenuated X-ray-radiation-induced endothelial dysfunction. CONCLUSION: Formononetin, the active component of RAS RH, mediates TCs-ECs crosstalk through the AR/miR-151a-5p/Fis1 axis, which represents the core mechanism for inhibiting excessive mitochondrial fission in ECs and alleviating EC injury.
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