Yan-Min Yang MM , Rong-Hua Shi MB , Chuan-Xiang Xu , Lei Li MB
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引用次数: 9
Abstract
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.
期刊介绍:
Cessation.
The Journal of the American Society of Hypertension (JASH) publishes peer-reviewed articles on the topics of basic, applied and translational research on blood pressure, hypertension and related cardiovascular disorders and factors; as well as clinical research and clinical trials in hypertension. Original research studies, reviews, hypotheses, editorial commentary and special reports spanning the spectrum of human and experimental animal and tissue research will be considered. All research studies must have been conducted following animal welfare guidelines. Studies involving human subjects or tissues must have received approval of the appropriate institutional committee charged with oversight of human studies and informed consent must be obtained.