ELEVATED CIRCULATING ENDOTHELIAL CELL-DERIVED MICROVESICLES: A BIOMARKER OF ENDOTHELIAL VASOMOTOR DYSFUNCTION IN ADULTS WITH OBESITY.

Abstract

Endothelial cell-derived extracellular microvesicles (EMVs) have emerged as a biomarker of cardiovascular disease risk, progression and severity. The aims were to determine: 1) if circulating EMV levels are elevated in adults with obesity; and 2) whether circulating EMVs are associated with obesity-related endothelial vasomotor dysfunction. Thirty-six sedentary, midlife adults (45-63 years) were studied: 18 adults with normal weight (12M/6F; age: 56±6 yr; BMI: 23.3±1.5 kg/m²) and 18 adults with obesity (12M/6F; 53±5 yr; 31.9±1.7 kg/m²). EMV (CD31⁺/42^-) concentration in plasma 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), sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) and the selective endothelin (ET)-1 receptor antagonist BQ-123 (ET_A receptor blockade; 100 nmol/min; for 60 min). Circulating EMVs were ~85% higher (P<0.001) in adults with obesity (147±54 EMV/μL) than adults with normal weight (79±27 EMV/mL). FBF response to acetylcholine was significantly lower (~30%) in adults with obesity (from 4.3±0.9 to 10.5±2.3 mL/100 mL tissue/min) vs adults with normal weight (from 4.2±0.9 to 15.1±2.4 mL/100 mL tissue/min). BQ-123 elicited a significantly greater (~35%) increase in FBF in adults with obesity, indicative of higher ET-1-mediated vasoconstrictor tone. Circulating EMVs were inversely related with total FBF response to acetylcholine (r=-0.49; P=0.001) and positively associated with total FBF response to BQ-123 (r=0.46; P=0.005). In conclusion, circulating levels of EMVs are elevated in adults with obesity and are associated with reduced endothelium-dependent vasodilation and increased ET-1 mediated vasoconstrictor tone.