Circulating Endothelial Cell-Derived Extracellular Vesicles Biomarker of Endothelial Vasomotor Dysfunction in Adults with Obesity
Authors: Wegerson Kendra , Fandl Hannah , Garcia Vinicius , Berry Auburn , Greiner Jared , Stauffer Brian , DeSouza Christopher 
Published: May 2023

The prevalence of obesity continues to increase in the United States, more than one-third of the adults in the United States have obesity. Experimental and clinical studies have shown that a proatherogenic endothelial phenotype is a major consequence of increased adiposity and underlies obesity-related cardiovascular disease (CVD). Clinical interest in circulating extracellular vesicles, particularly endothelial cell-derived microvesicles (EMVs), has increased given their potential pathogenic role in vascular dysfunction and CVD risk and events. We have previously demonstrated that elevated EMVs are associated with decreased endothelium-dependent vasodilation. In addition to diminished endothelial vasodilation, obesity is associated with increased endothelin (ET)-1-mediated vasoconstrictor tone. It is currently unknown if circulating EMVs is also linked to heightened ET-1 system activity in adults with obesity. Accordingly, the aim of this study was to determine if EMVs are associated with increased ET-1-mediated vasoconstrictor tone in adults with obesity. Thirty-six, mid-life adults (45-63 years) were studied: 18 normal weight (12M/6F; age: 56±1 yr; BMI: 23.3±0.4 kg/m2; body fat: 25.2±2.1 %) and 18 obese (12M/6F; age: 53±1 yr; BMI: 31.9±0.4 kg/m2; body fat: 38.7±1.6 %). All subjects were free of overt cardiometabolic disease. EMV identification (CD31+/CD42b-) and concentration in peripheral blood were determined by flow cytometry. Forearm blood flow (FBF: via plethysmography) was assessed in response to intra-arterial infusions of the selective ETA receptor blockade (BQ-123: 100 nmol/min for 60 min), acetylcholine (4.0, 8.0 and 16.0 mg/100 mL tissue/min) and sodium nitroprusside (1.0, 2.0 and 4.0 mg/100 mL tissue/min). Circulating EMV levels were ~75% higher (P<0.05) in adults with obesity (139±12 EMV/mL) compared with normal weight (79±6 EMV/mL) adults. BQ-123 elicited a significantly greater increase in FBF in adults with obesity (~30%) than normal weight (~2%) adults, indicative of greater ET-1-mediated vasoconstrictor tone. FBF response to acetylcholine was significantly lower (~30%) in the obese (from 4.3±0.2 to 10.6±0.6 mL/100 mL tissue/min) vs the normal weight (from 4.2±0.2 to 15.1±0.6 mL/100 mL tissue/min) group. There was no significant difference in FBF responses to sodium nitroprusside between the groups. Circulating EMVs were significantly and positively associated with the peak FBF response to BQ-123 (r=0.39) and inversely related with total FBF response to acetylcholine (r=-0.44). Higher circulating EMVs in adults with obesity represents a novel biomarker of endothelial vasomotor dysfunction and a potential mediator of impaired vascular function and disease risk. Nothing to disclose This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.