Abstract Using multiple mouse models, we explored the impact of aging on size and severity atherosclerotic lesions. In young, middle-aged old apolipoprotein E knockout mice (ApoE −/− ) fed an atherogenic diet (AD) for 3–8 weeks, plaque/atheroma formation in descending aorta aortic root, atheroma development carotid response to partial ligation (PCL) were assessed. Total LDL cholesterol, triglycerides higher compared both other age groups, regardless AD duration. Aortic plaque burden...

Increased large artery stiffness and impaired endothelium-dependent dilatation occur with advanced age. We sought to determine whether T cells mechanistically contribute age-related arterial dysfunction. found that old mice exhibited greater proinflammatory cell accumulation around both the aorta mesenteric arteries. Pharmacologic depletion or genetic deletion of in resulted ameliorated compared intact.

Atherosclerosis is the root cause of major cardiovascular diseases (CVD) such as myocardial infarction and stroke. ADP-ribosylation factor 6 (Arf6) a ubiquitously expressed GTPase known to be involved in inflammation, vascular permeability sensitive changes shear stress. Here, using atheroprone, ApoE -/- mice, with single allele deletion Arf6 (HET) or wildtype (WT), we demonstrate that reduction attenuates atherosclerotic plaque burden severity. We found descending aorta was lower HET...

Advanced age is the greatest risk factor for cardiovascular disease (CVD), leading cause of death. Arterial function impaired in advanced which contributes to development CVD. One underexplored hypothesis that DNA damage within arteries leads this dysfunction, yet evidence demonstrating incidence and physiological consequences arteries, particular, microvasculature, limited. In present study, we began by assessing abundance human mouse lung microvascular endothelial cells found aging...

The glycocalyx (GC) is a densely structured, gel-like matrix that coats the inner lining of vascular endothelium. GC plays pivotal role in regulating integrity endothelium, primarily through mechano-sensing and -transducing shear stress, while also preserving endothelial barrier function. With advancing age, deteriorates concomitantly with its essential constituent, hyaluronan (HA), which may lead to dysfunction. Therefore, we hypothesized advanced age reduced HA synthesis alone or together...

Abstract Endothelial dysfunction is associated with the racial health disparity in vascular African Americans (AAs). Matrix Metalloproteinase (MMP)-2 constitutively expressed endothelial cells (EC) and a biomarker that has been hypertension, as its properties are involved pathologic oxidative stress pro-inflammation may affect homeostasis. Herein , we report significant inverse relationships between MMP-2, stroke volume, carotid aortic systolic pressures small cohort of young AA men. In...

People with Type 2 Diabetes (T2D) often exhibit endothelial dysfunction (EndoDys), which underlies the initiation of many diseases. African Americans (AA) have a greater prevalence T2D and EndoDys than their Caucasian (CA) counterparts. To understand these differences, we examined glucose metabolism within endothelium. Specifically, sought to determine whether there are differences between AAs CAs in Hexosamine Biosynthesis Pathway (HBP), route utilization that is upregulated T2D. We...

The glycocalyx (GC) is a semi-solid layer lining the endothelium that plays key role in maintaining barrier function and mechanosensing shear forces. With advanced age pathological conditions, GC deteriorates, this accompanied by arterial dysfunction characterized impaired endothelial-dependent dilation (EDD) large elastic artery stiffening. Alterations hyaluronan (HA), primary component of GC, may contribute to development dysfunctional phenotype. Here, we sought determine HA integrity...

Matrix metalloproteinase (MMP)-2, an enzyme that is integral in regulating vascular structure and homeostasis, constitutively expressed endothelial cells (EC). MMP-2 has been associated with arterial stiffness hypertension African Americans (AA). While exercise improves biomarkers of dysfunction AA pre-hypertension hypertension, the mechanism(s) related to exercise-induced improvements EC health activity unknown. PURPOSE: To determine extent activity, its responsiveness a physiological...

Background Endothelial dysfunction is both a root cause and consequence of hypertension (HTN) cardiovascular diseases (CVD). It characterized by nitric oxide (NO) deficiency altered release vasoactive substances including inflammatory cytokines adhesion molecules. African Americans (AAs) have higher rates these vascular disruptions develop at than any other racial/ethnic group in the United States. C‐Reactive Protein (CRP) levels are greater AAs CRP has been shown, vitro, to promote...

Background MMP‐2 is a biomarker that has been associated with systolic hypertension and arterial stiffness African Americans (AA). Endothelial cells (EC) constitutively express MMP‐2, where it mediates extracellular matrix turnover, its dysfunction likely some role in vascular function. In small cohort of young AA Caucasian (CA) men, we have data showing an inverse moderate correlation between circulating carotid BP ( r =−0.555), aortic =−0.509) n =14) no relationship CA (n=18). this...

C-Reactive Protein (CRP) is an inflammatory biomarker linked to endothelial dysfunction, resulting hypertension, and cardiovascular events. 24-hr ambulatory blood pressure monitoring (ABPM) the gold standard for diagnosing with recent evidence showing a superior predictive value of asleep nighttime values, in particular, outcomes. PURPOSE: To assess whether circulating CRP levels differ between hypertensives normotensives examine ability exercise training affect levels. METHODS: Non-smoking,...

Hypertension (now defined by systolic blood pressure/diastolic pressure [SBP/DBP] greater than 130/90 mmHg), is one of the most common cardiovascular disorders and a critical public health economic concern. African Americans have greatest burden hypertension elucidating causes this racial disparity important for amending developing effective treatment strategies. Although studies provided mechanistic insight concerning characteristics endothelial dysfunction, which likely precedes in...

Blood pressure (BP) load is the percentage of BP readings above a particular threshold within given period. Elevated loads translate to organ exposures high pressures for greater amounts time. Because this, was heralded as strong predictor target damage (TOD). However, recent evidence has not confirmed its prognostic value 24 hr ambulatory blood monitoring (ABPM). Although questioned, it incorporated in AHA ABPM guidelines children and adolescents. Newer chronic kidney disease untreated...

BACKGROUND Inflammation enhances oxidative stress and plays a key role in the development of insulin resistance, diabetes (T2DM), endothelial dysfunction (ED), hypertension (HTN). The hexosamine biosynthesis pathway (HBP) vital cell health through protein activity, transcription, signaling. One stimulus for upregulation HBP is excessive stress, disruption glycolysis, ultimately an increase pathway’s substrates. Addition HBP’s end‐product onto proteins, creating β‐linked N‐acetylglucosamine...

Excessive addition of β-linked N-acetylglucosamine (O-GlcNAc) via the hexosamine biosynthesis pathway (HBP) occurs with diabetes and decreases in muscles exercise. HBP flux increases inflammation may be specifically important activation phase inflammatory response. Inflammation plays a key role insulin resistance hyperglycemia (HG), process contributing to development associated complications. β-cell differentiation are affected by HBP, O-GlcNAc has been indicated secretion from pancreas...

MicroRNAs (miRs) are short noncoding RNAs that regulate gene expression post-transcriptionally. It is well documented exercise improves endothelial function, possibly, by modifying flow-responsive miR (e.g. miRs-126*, -92-a and -21). MiR-126* an anti-atherogenic regulates vascular integrity, angiogenesis, inflammation. Whereas, miR-92a -21 pro-atherogenic miRs result in a reduction nitic oxide synthase (eNOS) activity. MiR-92a targets the transcription factor Kruppel-like 4 (KLF4) leading to...

Endothelial cells (ECs) are constantly exposed to hemodynamic shear stress that can influence vascular signaling. High laminar (HLSS), an exercise memetic, upregulates atheroprotective genes such as Kruppel-like factor 2 (KLF2), whereas disturbed flow and oscillatory SS upregulate proatherogenic adhesion molecule-1 (VCAM-1). Micro-RNAs (miRs) small non-coding RNAs regulate gene expression. Current evidence has identified mechano- sensitive miRs shear-induced expression ultimately control...