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.

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.

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.

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.

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.

The formation of the cell-free layer (CFL) near vessel walls plays a critical role in microcirculatory function, influencing blood rheology, oxygen delivery, and endothelial interactions. While hematocrit (Ht) is a well-established determinant of CFL thickness, the influence of shear-related parameters remains debated due to conflicting findings in the literature. In this study, we systematically quantified the optical CFL thickness (δ) in circular glass microchannels (25-50 μm diameter) under varying hematocrit levels (5-20 %), flow rates, and suspension media (phosphate-buffered saline and plasma). High-resolution microfluidic imaging and micro-particle image velocimetry (μPIV) were used to extract local velocity fields and calculate shear rate gradients (∇γ̇). Rather than treating ∇γ̇ as an imposed variable, we characterize it as a flow-derived descriptor of the local hydrodynamic environment. Across conditions, ∇γ̇ showed stronger correlations with CFL thickness than bulk shear rate. In PBS, increasing ∇γ̇ was associated with reduced CFL thickness, likely due to enhanced shear-induced dispersion. In contrast, in plasma, higher ∇γ̇ values promoted disaggregation of red blood cell (RBC) aggregates and restored hydrodynamic lift, resulting in thicker CFLs. These trends underscore the importance of considering both the suspension medium and spatial shear variations when interpreting RBC behavior. Comparison with prior in vitro, in vivo, and computational studies suggests that discrepancies in reported CFL trends can often be reconciled by accounting for differences in aggregation potential and local shear rate gradients. This work provides a unified experimental framework for interpreting CFL dynamics and highlights ∇γ̇ as a valuable parameter for describing flow-mediated RBC redistribution in the microcirculation.

To investigate the hypothesis that the wall-to-lumen ratio (WLR) of retinal arteries is predictive of morbidity and mortality in patients with end-stage chronic kidney disease (CKD).

Angiogenesis is critical for effective wound healing, supplying oxygen and nutrients to regenerating tissues. In chronic conditions like diabetes, impaired angiogenesis leads to delayed healing, chronic wounds, and significant healthcare burdens. Exosomes, nano-sized extracellular vesicles derived from cells such as mesenchymal stem cells (MSCs), amniotic epithelial cells, and keratinocytes, have emerged as key mediators in promoting angiogenesis. Laden with bioactive cargos-including microRNAs, proteins, and lipids-exosomes orchestrate endothelial cell proliferation, migration, and extracellular matrix remodeling to enhance vascularization. This review explores the molecular mechanisms by which exosomes drive angiogenesis, highlighting their role in modulating signaling pathways and immune responses critical for tissue repair. We evaluate the therapeutic promise of exosome-based delivery systems, integrating insights from biological, pharmaceutical, and cell-based approaches. By leveraging these advancements, exosomal therapies offer transformative potential for managing chronic wounds and ischemic conditions, paving the way for innovative regenerative medicine strategies.

Peripheral artery disease (PAD) is a global health challenge, with current diagnostic methods, including the ankle-brachial index (ABI), having limitations, particularly in patients with arterial calcification. Near-infrared spectroscopy (NIRS) offers potential advantages as a non-invasive assessment tool, yet its clinical utility in PAD remains underexplored. This pilot study evaluated NIRS for differentiating between non-ischemic upper limbs and ischemic lower limbs, and assessed NIRS correlation with ABI. To do that, we performed an observational, cross-sectional study employing a convenience sample of 51 patients with PAD attending the vascular surgery outpatient clinic. A portable spectrometer recorded NIRS measurements from the right thumb and both halluces at rest. Random Forest classification was implemented to differentiate upper and lower limbs, revealing distinct NIRS patterns between upper and lower limbs, with an area under the ROC curve of 0.91 (95 % CI 0.88-0.94). Interval Partial Least Squares regression (iPLS) identified wavelength regions correlating with ABI, with the 1429-1463 nm interval being the most informative for ABI prediction, with a modest correlation (R = 0.167, RMSECV = 0.186). NIRS demonstrated strong discriminative capability between non-ischemic upper and ischemic lower limbs in PAD. While the correlation between NIRS and ABI was modest, it suggests potential clinical relevance. These findings indicate that NIRS could be a rapid, portable, non-invasive complementary tool for PAD assessment.

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.

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.

Diabetes mellitus (DM) has been associated with coronary microvascular dysfunction (CMD) in previous non-invasive studies. However, invasive studies have shown conflicting results.

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.

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.

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).

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.

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.

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).

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.

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.