Role of eNOS- and NOX-containing microparticles in endothelial dysfunction in patients with obesity

Abstract

Objective: To explore the pathophysiological profile of patients who have obesity and to investigate the potential role of circulating microparticles (MPs) in endothelial dysfunction in patients who have obesity. Methods: The inflammatory and oxidative status and the cutaneous microvascular blood flow were characterized in 69 patients with android obesity and 46 subjects with normal weight (controls) by using laser Doppler flowmetry. Circulating MP levels were measured by flow cytometry, and endothelial nitric oxide synthase (eNOS) and NADPH oxidase (NOX) expression in MPs was investigated by Western blotting. MP effect on vascular reactivity was assessed in rat aorta rings. Results: Patients with obesity showed endothelial dysfunction, hyperglycemia, inflammation, and oxidative stress. In controls, low MP levels were positively correlated with normal microvascular function. Western blot analysis revealed reduced eNOS and increased NOX4D expression in MPs from subjects with obesity compared with controls. However, this was not correlated with endothelial dysfunction parameters and did not impair ex vivo endothelium-dependent vasodilation. Conclusions: These results suggest that MPs do not contribute directly to endothelial dysfunction associated with obesity. Conversely, eNOS- and NOX-containing MPs could be involved in the compensatory mechanism of vascular endothelial cells to counteract the pathologic mechanisms underlying endothelial dysfunction.