MicroRNA-21 Contributes to Reduced Microvascular Function in Binge Drinking Young Adults.

Abstract

Binge drinking is associated with increased risk for cardiovascular (CV) disease. MicroRNA-21 (miR21) is up-regulated in the setting of excessive alcohol consumption and CV disease. Therefore, the goal of this study was to examine the vasodilatory responses to flow and acetylcholine (ACh) in the absence and presence of an anti-miR21 inhibitor in the microcirculation of young adult repeated binge drinkers (BDs). Gluteal subcutaneous adipose tissue biopsies were obtained from young adults (18 to 30years, n=35 vessels from BDs and n=28 vessels from abstainers). Resistance arteries (RAs) were isolated, incubated with anti-miR21 or a negative control (NC) to miR21 (12hours; 50nM), and lumen diameters measured with video microscopy. miR21 of adipose tissues was determined by quantitative polymerase chain reaction. Flow-induced dilation and ACh-induced dilation (AChID) were reduced in BDs as compared to abstainers. The miR21 inhibitor but not the NC abrogated these effects in BDs, but did not affect vasodilation in abstainers. Nitric oxide synthase inhibition with L-NAME reduced vasodilation in abstainers but not in BDs. In BDs, vasodilation was reduced by L-NAME in the presence of anti-miR21 but not the NC. Scavenging the reactive oxygen species, hydrogen peroxide with polyethylene glycol catalase reduced dilation in BDs but did not affect the restored dilation by the miR21 inhibitor. Maximum dilation to papaverine (endothelium independent) was similar between groups and unaffected by pharmacological inhibition. Finally, vascular endogenous miR21 was increased in BDs compared to abstainers. Endogenous miR21 is increased in RAs of young BDs, leading to reduced flow and AChID in the microcirculation.