Abstract
Background: Aging is associated with a progressive increase in risk and prevalence of cardiovascular disease (CVD). Endothelial cell dysfunction is considered to be a central mechanism underlying the age-related increase in vascular risk and disease. However, the direct, and indirect, effects of aging on endothelial cell biology are diverse and not completely understood.Clinical interest in circulating extracellular vesicles, particularly endothelial cell-derived microvesicles (EMVs), has intensified due to their involvement in 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. Methods: Thirty-six healthy, non-obese, normotensive, sedentary men were studied: 12 young (age: 27 + 1 yr); 12 middle-aged (51 + 1 yr) and 12 older (67 + 2 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 (4.0, 8.0 and 16.0 μg/100 mL tissue/min) and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) in 8 young, 8 middle-aged and 8 older men. Results: Circulating EMV levels were significantly and progressively higher across the young, middle-aged and older groups (57 + 5 vs 102 + 9 vs 134 + 16 EMV/μL, respectively). FBF response to acetylcholine was significantly and progressively lower (~35%) in the young (from 5.2±0.4 to 17.2±1.8 mL/100 mL tissue/min) vs middle-aged (4.5±0.3 to 13.2±1.2 mL/100 mL tissue/min) vs older (4.2±0.3 to 11.3±0.8 mL/100 mL tissue/min) group. Circulating EMVs were positively associated with age (r=0.67; P<0.01) and inversely associated with the vasodilator response to acetylcholine (r=-0.43; P<0.01). Conclusions: Aging, independent of other cardiometabolic risk factors, is associated with progressive elevated circulating levels of EMVs. Circulating EMVs may serve as a biomarker of, and contributor to, age-related endothelial dysfunction and vascular disease risk.
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