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

MicroRNA-21 Contributes to Reduced Microvascular Function in Binge Drinking Young Adults.
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DOI:
10.1111/acer.13565
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发表时间:
2018-03
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
通讯作者:
Phillips SA
Phillips SA
中科院分区:
其他
文献类型:
--
作者:
Bian JT;Piano MR;Kotlo KU;Mahmoud AM;Phillips SA

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酗酒与心血管(CV)疾病的风险增加有关。microRNA-21(miR 21)在过量饮酒和CV疾病的情况下上调。因此,本研究的目的是检查在年轻成人反复酗酒者的微循环中存在和不存在抗miR 21抑制剂的情况下对流量和乙酰胆碱的血管舒张反应。从年轻人(18-30岁,n = 35条血管来自酗酒者[BD],n = 28条血管来自戒酒者)中获得臀部皮下脂肪组织活检。分离阻力动脉(RA),用抗miR-21或miR-21的阴性对照孵育(12小时; 5 nM),并用视频显微镜测量管腔直径。采用定量PCR(qPCR)检测脂肪组织中的miRNA-21。血流诱导的血管扩张(FID)和乙酰胆碱(ACh)诱导的血管扩张(AChID)减少,在BD相比,弃权。miR-21抑制剂而非阴性对照消除了BD中的这些作用,但不影响戒断者的血管舒张。用L-NAME抑制一氧化氮合酶可减少戒断者的血管舒张,但在BD中则不然。在BD中,在存在抗miR-21的情况下,L-NAME降低了血管舒张,但阴性对照没有。用聚乙二醇-过氧化氢酶清除活性氧过氧化氢减少了BD的扩张,但不影响miR-21抑制剂恢复的扩张。罂粟碱的最大扩张(非内皮依赖性)在组间相似,不受药理学抑制的影响。最后,与戒断者相比,BD中血管内源性miR-21增加。内源性microRNA-21在年轻BD的RA中增加,导致微循环中的流量减少和乙酰胆碱诱导的血管舒张。
Binge drinking is associated with increased risk for cardiovascular (CV) disease. MicroRNA-21 (miR21) is upregulated 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 in the absence and presence of an anti-miR21 inhibitor in the microcirculation of young adult repeated binge drinkers. Gluteal subcutaneous adipose tissue biopsies were obtained from young adults (18–30 yrs, n = 35 vessels from binge drinkers [BDs] and n = 28 vessels from abstainers). Resistance arteries (RAs) were isolated, incubated with anti-miR21 or a negative control to miR-21 (12 hours; 5 nM), and lumen diameters measured with video microscopy. MiRNA-21 of adipose tissues was determined by quantitative PCR (qPCR). Flow-induced dilation (FID) and acetylcholine (ACh)-induced dilation (AChID) were reduced in BDs as compared to abstainers. The miR-21 inhibitor but not the negative control 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-miR-21 but not the negative control. Scavenging the reactive oxygen species hydrogen peroxide with polyethyleneglyco-catalase reduced dilation in BDs but did not affect the restored dilation by miR-21 inhibitor. Maximum dilation to papaverine (endothelium-independent) was similar between groups and unaffected by pharmacological inhibition. Finally, vascular endogenous miR-21 was increased in BDs compared to abstainers. Endogenous microRNA-21 is increased in RAs of young BDs, leading to reduced flow and acetylcholine-induced vasodilation in the microcirculation.
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