Circulating Endothelial Extracellular Vesicles Progressively Increase With Age And Are Associated With Endothelial Vasodilator Dysfunction.
Journal Article
Overview
abstract
Aging is associated with a progressive increase in risk and prevalence of cardiovascular disease (CVD). Circulating extracellular vesicles, particularly endothelial cell-derived microvesicles (EMVs), have been linked to the development and progression of endothelial dysfunction and CVD. The purpose of this study was to determine: 1) if circulating EMV levels increase with age, independent of other cardiometabolic risk factors; and if so, 2) whether circulating EMVs are associated with age-related endothelial vasodilator dysfunction. Forty healthy, non-obese, normotensive, sedentary males were studied: 12 young (age: 27+5 yr); 14 midlife (51+5 yr) and 14 older (67+5 yr). EMV identification (CD31+/42b-) and concentration in peripheral blood was determined by flow cytometry. Forearm blood flow (FBF: via plethysmography) was assessed in response to intra-arterial infusions of acetylcholine and sodium nitroprusside. Circulating EMV levels were significantly and progressively higher across the young, midlife and older groups (54+14 vs 101+30 vs 132+54 EMV/μL, respectively). FBF response to acetylcholine was significantly lower (~30%) in the midlife (4.5±0.8 to 13.5±3.3 mL/100 mL tissue/min) and older (4.2±1.0 to 11.5±2.8 mL/100 mL tissue/min) vs young (from 5.2±1.1 to 17.2±4.9 mL/100 mL tissue/min) group. Circulating EMVs were positively associated with age (r=0.68; P<0.001) and inversely associated with endothelial vasodilation (peak FBF to acetylcholine: r=-0.51; and total FBF to acetylcholine: r=-0.48; P=0.02). Aging, independent of other cardiometabolic risk factors, is associated with progressive elevated circulating levels of EMVs in healthy males. Circulating EMVs may serve as a biomarker of, and potential contributor to, age-related endothelial dysfunction and vascular disease risk.
