Journal of Vascular Research最新文献

Introduction: Investigation into vascular health and disease across elevated risk conditions has been intensively studied for many years. However, the ability to understand integrated vascular health status has been challenging, as most previous work has focused on specific outcomes, interventions, or potential mechanistic links. While these efforts have revealed many factors contributing to vasculopathy, challenges remain for comparing results across research groups, models, and conditions to understand vascular health status. In the present study, our objective was to quantify sex-dependent differences in peripheral and cerebral vascular health across metabolic disease.

Methods: Utilizing the vascular health index (VHI), a validated metric allowing for simultaneous assessment of vascular reactivity/endothelial function, vascular wall mechanics, and microvessel density within cerebral and skeletal muscle networks, we focus on the impact of elevated metabolic disease risk between male and female obese Zucker rats (OZR). In addition, we study VHI in female OZR following ovariectomy (OVX), with all outcomes compared to results from "healthy" lean Zucker rats (LZRs).

Results: Across all ages, male and female LZR demonstrated comparable VHI, although increased metabolic disease risk reduced both skeletal muscle and cerebral VHI in male OZR more rapidly, and to a greater extent, as compared to female OZR. Protection for VHI for female OZR with elevated disease risk was dependent on intact sex hormone cycling, as OVX in female OZR removed protection in VHI compared to normal female OZR.

Conclusion: These results indicate that sex-based protections in peripheral and cerebral vascular health with metabolic disease in female OZR (versus males) are present at multiple levels of resolution and are dependent on normal female sex hormone cycling.

Introduction: The role of dietary antioxidants in preventing or delaying the progression of cardiovascular-kidney-metabolic (CKM) syndrome remains underexplored. We aimed to develop and interpret a machine learning (ML) model to predict advanced CKM stages based on dietary antioxidant profiles.

Methods: Data were analyzed from 10,257 adults aged >30 years in the NHANES 2007-2010 and 2017-2018 cycles. Dietary antioxidant intake was estimated using two 24-h dietary recalls. Five ML algorithms were trained with rigorous hyperparameter optimization and evaluated comprehensively. SHapley Additive exPlanations (SHAP) was applied to elucidate feature importance and individual-level contributions. An online prediction tool was deployed to enhance clinical utility.

Results: The eXtreme Gradient Boosting (XGBoost) model achieved the highest predictive performance, yielding an area under the curve of 0.901. SHAP analysis identified seven key predictors: age, sex, smoking status, magnesium, zinc, myricetin, and catechin. Older age, male sex, and smoking were associated with increased CKM risk, whereas higher intakes of magnesium, myricetin, zinc, and catechin were protective.

Conclusions: XGBoost effectively predicted advanced CKM stages using a concise set of seven features. Explainable AI approaches such as SHAP enhance model transparency and clinical translation, supporting personalized CKM risk stratification based on dietary antioxidant patterns.

Background: The impairment of vascular smooth muscle cells (VSMCs) causes many vascular diseases, such as atherosclerosis, hypertension, and heart conditions. Research has shown that N6-methyladenosine (m6A) modification regulates VSMCs' function in a vascular environment.

Summary: By regulating RNA metabolism, m6A modification affects key biological processes in VSMCs, such as proliferation, migration, phenotypic transformation, and apoptosis. We aim to examine the role of m6A modification and its associated enzymes in vascular diseases caused by VSMC dysfunction and explore its potential as a therapeutic target so that we can develop drugs targeting VSMC dysfunction on a scientific basis.

Key messages: m6A modification's role in cardiovascular disorders and potential as a therapeutic target demand further study as a critical regulating component in VSMC biology.

Introduction: Smooth muscle cells (SMCs) with an origin separate from the local vein wall contribute to formation of intimal hyperplasia (IH) in mouse vein grafts. The recruitment pathway of these cells has not been defined, but circulating progenitor cells and cells from the surrounding tissue or adjacent artery to which the vein graft is anastomosed are potential sources. The aim of this study was to clarify if cells from the adjacent artery contribute to neointimal formation in vein grafts.

Methods: Aortic segments from donor SM22α-LacZ mice were anastomosed to vein segments from wild-type (WT) C57BL/6 mice ex vivo followed by implantation of the composite grafts to the right common carotid arteries of WT recipient mice. Six weeks after surgery, the composite grafts were harvested, and histology was analyzed in longitudinal sections. SMCs with origin in the SM22α-LacZ arterial segments were identified with X-gal staining.

Results: LacZ-positive cells were found in the medial layer of the SM22α-LacZ arterial segments but were not found in the IH in the vein graft segment.

Conclusion: SMCs in vein grafts are not recruited from the adjacent artery through migration across the anastomosis.

Introduction: Unstable human artery plaques can suddenly rupture, leading to MI or stroke. Identification of blood markers associated with unstable plaque features is clearly needed. Humans with symptomatic carotid atherosclerotic plaques have increased infiltration of CD56bright natural killer (NK) cells into the plaque, yet whether subjects with unstable coronary artery plaque features have increased frequencies of circulating CD56bright NK cells is unknown.

Methods: Coronary artery intravascular ultrasound (IVUS) was performed on subjects presenting for medically indicated coronary angiography. Eighteen subjects stratified into high and low percent (%) necrotic core and matched for age, body mass index (BMI), and lipids underwent mass cytometry by time-of-flight analysis on their peripheral blood mononuclear cells collected prior to imaging. Clustering of major immune cell populations was performed on live singlets and CD56 bright and dim NK subsets were quantitated.

Results: Subjects with high necrotic core had a significantly greater frequency of circulating CD56bright NK cells compared to subjects with low necrotic core (p = 0.02). Additionally, the frequency of circulating CD56bright NK cells positively associated with IVUS-VH metrics of total atheroma volume (p = 0.0013), percent (%) atheroma burden (p = 0.0048), % maximum stenosis (p = 0.0021), % necrotic (p = 0.0013), % calcium (p = 0.0016), % fatty (p = 0.0097) and negatively associated with % fibrous (p < 0.0001), an IVUS-VH metric of plaque stability.

Conclusion: These findings suggest that the frequency of CD56bright NK cells may be a safe, noninvasive marker of plaque volume and instability.

Introduction: The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a factor X inhibitor, on the glycocalyx under oxidative stress condition.

Methods: We examined the impact of rivaroxaban on human umbilical vein endothelial cells exposed to acute and chronic H2O2-induced oxidative stress.

Results: Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx.

Conclusion: We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.

Introduction: The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a factor X inhibitor, on the glycocalyx under oxidative stress condition.

Methods: We examined the impact of rivaroxaban on human umbilical vein endothelial cells exposed to acute and chronic H2O2-induced oxidative stress.

Results: Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx.

Conclusion: We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.

Introduction: Exploring the association between oxidative balance score (OBS) and all-cause mortality in hypertension (HTN).

Methods: Data for HTN patients from 2007 to 2018 were extracted from the National Health and Nutrition Examination Survey (NHANES). OBS offers a thorough evaluation of an individual's redox status, with higher score indicates favorable oxidative homeostasis. All-cause mortality was obtained by linkage to National Death Index records through 31 December 2019. Weighted multivariable Cox regression models, Kaplan-Meier curves, receiver operator characteristic curve, and random survival forests (RSF) analysis were applied to examine the relationship between OBS and all-cause mortality in HTN.

Results: The cohort included 13,130 participants, with 2,132 deaths. Higher OBS was associated with lower all-cause mortality risk (HR = 0.77, 95% CI: 0.65-0.91) in HTN. The relationship also existed in subgroups of male, having/have not chronic kidney disease, and having cardiovascular disease. Kaplan-Meier curves suggested that participants with higher OBS had superior survival rates compared to those with lower intake. The RSF showed a better survival predictive role for physical activity among the components of OBS.

Conclusion: Higher OBS was related to lower odds of all-cause mortality in patients with HTN. Adopting a healthy lifestyle and consuming an antioxidant-rich diet may improve the prognosis of patients with HTN.

Introduction: We investigated the effects of transfusing blood products close to the expiration date (i.e., ≥35 days packed red blood cells [PRBCs] and >3 days platelets [PLTs]) on vascular patients.

Methods: We retrospectively examined all PRBC and PLT transfusions in patients who underwent vascular procedures without cardiopulmonary bypass in Queensland from 2007 to 2013. Mortality, length of stay (LOS), and blood product quantities were compared in patients transfused exclusively with PRBCs <21 days vs. PRBCs ≥35 days and PLTs ≤3 days vs. PLTs >3 days.

Results: No significant mortality difference was found between patients transfused fresh vs. old PRBCs (26/493 [5.3%] vs. 6/152 [3.9%]; OR 0.75; 95% CI: 0.3-1.9). Patients transfused fresh PRBCs experienced a longer LOS (11 days [IQR: 7-20] vs. 10 days [IQR: 7-15]; 95% CI: -4.8 to -0.24) and more PRBC units (3.9 ± 4.5 units vs. 2.1 ± 1.3 units; 95% CI: -2.3 to -0.9). Among patients transfused PLTs, there were no significant differences in mortality (24/124 [19.4%] vs. 14/78 [17.9%]; OR 1.0; 95% CI: 0.5-2.3) between patients transfused fresh vs. old PLTs.

Conclusion: Within the limitations of the retrospective study design, transfusion of older PRBCs or PLTs was associated with fewer transfused units, shorter hospital stays, but no difference in mortality.