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 yr) were studied: 18 adults with normal weight (12 M/6 F; age: 56 ± 6 yr; body mass index: 23.3 ± 1.5 kg/m²) and 18 adults with obesity (12 M/6 F; 53 ± 5 yr; 31.9 ± 1.7 kg/m²). EMV (CD31⁺/42b^-) 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 in adults with normal weight (79 ± 27 EMV/µL). 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) versus 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.NEW & NOTEWORTHY Circulating endothelial microvesicles (EMVs) may serve as a key biomarker and mediator of vascular dysfunction in obesity. This study demonstrates that EMV levels are markedly higher in adults with obesity compared with adults with normal weight. Elevated EMVs were associated with impaired endothelial vasodilation and heightened endothelin-1-mediated vasoconstriction. These findings highlight a potential mechanistic link between obesity and cardiovascular disease risk, emphasizing the role of EMVs in vascular health.

Keywords: endothelial microvesicles; endothelium; obesity; vasoconstriction; vasodilation.