Apoptosis derived but not activation derived EMV are predictive of arterial stiffness

• Grifffin Edwards, Human Physiology, Wagner College

• David Edwards, Kinesiology and Applied Physiology, University of Delaware

Endothelial derived microvesicles (EMVs) are a nontraditional marker of vascular aging and risk for cardiovascular disease (CVD). EMVs released during endothelial activation and apoptosis are indicative of endothelial characteristics and can alter vascular function after release. Large artery stiffness, a contributor to CVD, is composed of structural (intrinsic components of the wall) and load-dependent factors (arterial blood pressure). We hypothesized that EMVs were associated with structural and load-dependent components of arterial stiffness. Venous blood samples were collected from forty-two young (7M/7F, 26.5±2.7 y/o), midlife (7M/7F, 48.9±6.4 y/o), and older (6M/8F, 66.7±5.0 y/o) healthy adults. Platelet-free plasma was incubated with fluorochrome-labeled antibodies (anti-CD31-APC and anti-CD42b-PE or anti-CD62e-APC). Samples were analyzed with nanoscale flow cytometry (CytoFLEX LX). Events between 200 and 900 nm in size that were CD31+ /CD42b- or CD62e+ were considered as large apoptosis-derived EMVs or large activation-derived EMVs, respectively. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (CF-PWV). Participant-specific exponential models were standardized to a reference blood pressure in order to separate structural and load-dependent stiffness components. Linear regression was used to assess the ability of EMV subtypes to predict PWV and the structural and load-dependent components of stiffness. Linear regression showed that apoptosis-derived EMVs were associated with PWV (r2=0.13, p=0.018) and structural arterial stiffness (r2=0.11, p=0.028) whereas activation-derived EMVs were not associated with PWV or structural stiffness but tended to be associated with load dependent stiffness (p=0.061). These data suggest that apoptosis-derived EMVs may serve as a marker for arterial stiffness and vascular health. Future research should focus on the mechanisms by which EMVs may increase arterial stiffness.