Department of Biobehavioral Health Science, University of Illinois at Chicago, Chicago, Illinois.
School of Nursing, Vanderbilt University, Nashville, Tennessee.
Alcohol Clin Exp Res. 2018 Feb;42(2):278-285. doi: 10.1111/acer.13565. Epub 2017 Dec 27.
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 30 years, 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 (12 hours; 50 nM), 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.
binge drinking（狂饮）与心血管疾病风险增加相关。在过度饮酒和心血管疾病的情况下，microRNA-21（miR21）上调。因此，本研究的目的是在年轻成年反复 binge drinkers（BDs）的微血管中，在不存在和存在抗 miR21 抑制剂的情况下，检测血流和乙酰胆碱（ACh）引起的血管舒张反应。
从年轻成年人（18 至 30 岁，BDs 组 35 个血管， Abstainers 组 28 个血管）获得臀下皮下脂肪组织活检。分离阻力动脉（RAs），用抗 miR21 或 miR21 阴性对照（NC）孵育（12 小时；50 nM），并用视频显微镜测量管腔直径。用定量聚合酶链反应测定脂肪组织中的 miR21。
与 Abstainers 相比，BDs 中的血流诱导舒张和 ACh 诱导舒张（AChID）降低。miR21 抑制剂而非 NC 消除了 BDs 中的这些作用，但对 Abstainers 中的血管舒张没有影响。用 L-NAME 抑制一氧化氮合酶减少了 Abstainers 中的血管舒张，但对 BDs 没有影响。在 BDs 中，L-NAME 降低了抗 miR21 而不是 NC 的血管舒张。用聚乙二醇过氧化氢酶清除活性氧、过氧化氢减少了 BDs 的舒张，但对 miR21 抑制剂恢复的舒张没有影响。与 abstainers 相比，各组对罂粟碱（内皮非依赖性）的最大舒张相似，不受药物抑制的影响。最后，与 abstainers 相比，BDs 中的血管内源性 miR21 增加。
年轻 BDs 的 RA 中内源性 miR21 增加，导致微血管中血流和 AChID 减少。
