Laboratory of Cardiovascular Pathology, Bristol Medical School, University of Bristol, UK.
Vascul Pharmacol. 2019 Mar;114:31-48. doi: 10.1016/j.vph.2018.10.010. Epub 2018 Oct 31.
Cardiovascular diseases encompassing atherosclerosis, aortic aneurysms, restenosis, and pulmonary arterial hypertension, remain the leading cause of morbidity and mortality worldwide. In response to a range of stimuli, the dynamic interplay between biochemical and biomechanical mechanisms affect the behaviour and function of multiple cell types, driving the development and progression of cardiovascular diseases. Accumulating evidence has highlighted microRNAs (miRs) as significant regulators and micro-managers of key cellular and molecular pathophysiological processes involved in predominant cardiovascular diseases, including cell mitosis, motility and viability, lipid metabolism, generation of inflammatory mediators, and dysregulated proteolysis. Human pathological and clinical studies have aimed to identify select microRNA which may serve as biomarkers of disease and their progression, which are discussed within this review. In addition, I provide comprehensive coverage of in vivo investigations elucidating the modulation of distinct microRNA on the pathophysiology of atherosclerosis, abdominal aortic aneurysms, restenosis, and pulmonary arterial hypertension. Collectively, clinical and animal studies have begun to unravel the complex and often diverse effects microRNAs and their targets impart during the development of cardiovascular diseases and revealed promising therapeutic strategies through which modulation of microRNA function may be applied clinically.
心血管疾病包括动脉粥样硬化、主动脉瘤、再狭窄和肺动脉高压,仍然是全球发病率和死亡率的主要原因。在一系列刺激下,生化和生物力学机制的动态相互作用影响多种细胞类型的行为和功能,推动心血管疾病的发展和进展。越来越多的证据表明,microRNAs(miRs)是涉及主要心血管疾病的关键细胞和分子病理生理过程的重要调节剂和微观管理者,包括细胞有丝分裂、运动性和活力、脂质代谢、炎症介质的产生以及失调的蛋白水解。人类病理和临床研究旨在确定可能作为疾病及其进展标志物的特定 microRNA,本文对此进行了讨论。此外,我还全面介绍了阐明不同 microRNA 对动脉粥样硬化、腹主动脉瘤、再狭窄和肺动脉高压病理生理学调节的体内研究。总的来说,临床和动物研究已经开始揭示 microRNAs 及其靶标在心血管疾病发展过程中所产生的复杂且往往多样的影响,并揭示了有希望的治疗策略,通过这些策略可以在临床上应用 microRNA 功能的调节。