当前位置: X-MOL 学术J. Am. Soc. Hypertens. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
BRD4 expression in patients with essential hypertension and its effect on blood pressure in spontaneously hypertensive rats
Journal of the American Society of Hypertension Pub Date : 2018-11-22 , DOI: 10.1016/j.jash.2018.11.004
Yan-Min Yang , Rong-Hua Shi , Chuan-Xiang Xu , Lei Li

The objective of this study was to investigate BRD4 expression in patients with essential hypertension (EH) and its effects on the blood pressure in spontaneously hypertensive (SHR) rats. BRD4 expression was detected by quantitative real-time polymerase chain reaction and western blot in 163 patients with EH and its relation to systolic blood pressure and diastolic blood pressure were analyzed accordingly. In vivo, rats were divided into WKY (Wistar-Kyoto rats), SHR (spontaneously hypertensive rats), SHR + JQ1 (BRD4 inhibitor), and SHR + Vehicle control. Rats' blood pressure was measured by the tail-cuff method. The protein expressions related to inflammation and oxidative stress of rats were determined. BRD4 was higher in patients with EH than healthy controls, which was positively correlated to systolic blood pressure and diastolic blood pressure of enrolled subjects including patients with EH and healthy controls. Rats in the SHR group showed reduced food-intake, decreased body weight, and gradually increased blood pressure compared with WKY group. Besides, SHR rats were upregulated in plasma levels of Ang II, ET-1, MDA, IL-6, and TNF-α, and substantially downregulated in NO, NOS, and SOD levels. Moreover, eNOS activity in aortic tissues of SHR rats declined obviously, whereas the content of nitrite and O2, the activity of NADPH oxidase and NADH oxidase, and the expression of p-NF-κB p65 went up statistically, which could be partially reversed by JQ1. BRD4 was highly expressed in patients with EH, and inhibiting BRD4 could reduce oxidative stress and inflammatory response, alleviate endothelial cell damage, ameliorate aortic injury, and lower blood pressure, supporting the hypothesis that BRD4 inhibition could be a potential target for the clinical treatment of patients with EH.



中文翻译:

自发性高血压大鼠原发性高血压患者BRD4的表达及其对血压的影响

这项研究的目的是研究原发性高血压(SHR)大鼠原发性高血压(EH)患者中BRD4的表达及其对血压的影响。采用定量实时聚合酶链反应和western blot检测163例EH患者的BRD4表达,并分析其与收缩压和舒张压的关系。在体内,将大鼠分为WKY(Wistar-Kyoto大鼠),SHR(自发性高血压大鼠),SHR + JQ1(BRD4抑制剂)和SHR +媒介物对照。通过尾套法测量大鼠的血压。测定与大鼠炎症和氧化应激相关的蛋白质表达。EH患者的BRD4高于健康对照组,这与包括EH和健康对照组在内的入选受试者的收缩压和舒张压呈正相关。与WKY组相比,SHR组的大鼠食物摄入减少,体重减轻并且血压逐渐升高。此外,SHR大鼠血浆Ang II,ET-1,MDA,IL-6和TNF-α的水平上调,而NO,NOS和SOD的水平则下调。此外,SHR大鼠主动脉组织中的eNOS活性明显下降,而亚硝酸盐和O的含量 并大幅下调了NO,NOS和SOD含量。此外,SHR大鼠主动脉组织中的eNOS活性明显下降,而亚硝酸盐和O的含量 并大幅下调了NO,NOS和SOD含量。此外,SHR大鼠主动脉组织中的eNOS活性明显下降,而亚硝酸盐和O的含量2 -,NADPH氧化酶和NADH氧化酶,和对NF-κBp65蛋白的表达的活性上升统计学,这可以通过JQ1被部分颠倒。BRD4在EH患者中高表达,抑制BRD4可以减轻氧化应激和炎症反应,减轻内皮细胞损伤,改善主动脉损伤,降低血压,支持BRD4抑制可能成为临床治疗潜在目标的假设。 EH患者。

更新日期:2018-11-22
down
wechat
bug