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高血压的药物-表观遗传学:以 microRNA 为重点。

The pharmaco-epigenetics of hypertension: a focus on microRNA.

机构信息

Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar.

出版信息

Mol Cell Biochem. 2024 Dec;479(12):3255-3271. doi: 10.1007/s11010-024-04947-9. Epub 2024 Feb 29.

Abstract

Hypertension is a major harbinger of cardiovascular morbidity and mortality. It predisposes to higher rates of myocardial infarction, chronic kidney failure, stroke, and heart failure than most other risk factors. By 2025, the prevalence of hypertension is projected to reach 1.5 billion people. The pathophysiology of this disease is multifaceted, as it involves nitric oxide and endothelin dysregulation, reactive oxygen species, vascular smooth muscle proliferation, and vessel wall calcification, among others. With the advent of new biomolecular techniques, various studies have elucidated a gaping hole in the etiology and mechanisms of hypertension. Indeed, epigenetics, DNA methylation, histone modification, and microRNA-mediated translational silencing appear to play crucial roles in altering the molecular phenotype into a hypertensive profile. Here, we critically review the experimentally determined associations between microRNA (miRNA) molecules and hypertension pharmacotherapy. Particular attention is given to the epigenetic mechanisms underlying the physiological responses to antihypertensive drugs like candesartan, and other relevant drugs like clopidogrel, aspirin, and statins among others. Furthermore, how miRNA affects the pharmaco-epigenetics of hypertension is especially highlighted.

摘要

高血压是心血管发病率和死亡率的主要先兆。与大多数其他危险因素相比,高血压更容易导致心肌梗死、慢性肾衰竭、中风和心力衰竭的发生率升高。到 2025 年,预计高血压患者将达到 15 亿人。这种疾病的病理生理学是多方面的,因为它涉及一氧化氮和内皮素失调、活性氧、血管平滑肌增殖和血管壁钙化等。随着新的生物分子技术的出现,各种研究已经阐明了高血压病因和机制中的一个巨大空白。实际上,表观遗传学、DNA 甲基化、组蛋白修饰和 microRNA 介导的翻译沉默似乎在将分子表型改变为高血压表型方面发挥着关键作用。在这里,我们批判性地回顾了 miRNA(microRNA)分子与高血压药物治疗之间的实验确定关联。特别关注了坎地沙坦等抗高血压药物以及氯吡格雷、阿司匹林和他汀类药物等其他相关药物的生理反应背后的表观遗传机制。此外,还特别强调了 miRNA 如何影响高血压的药物表观遗传学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/11511726/68f20aaafc39/11010_2024_4947_Fig1_HTML.jpg

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