Komal Sumra, Han Sheng-Na, Cui Liu-Gen, Zhai Miao-Miao, Zhou Yue-Jiao, Wang Pei, Shakeel Muhammad, Zhang Li-Rong
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Pharmaceuticals (Basel). 2023 Jan 18;16(2):141. doi: 10.3390/ph16020141.
Cardiovascular diseases (CVDs) are the leading cause of hospitalization and death worldwide, especially in developing countries. The increased prevalence rate and mortality due to CVDs, despite the development of several approaches for prevention and treatment, are alarming trends in global health. Chronic inflammation and macrophage infiltration are key regulators of the initiation and progression of CVDs. Recent data suggest that epigenetic modifications, such as DNA methylation, posttranslational histone modifications, and RNA modifications, regulate cell development, DNA damage repair, apoptosis, immunity, calcium signaling, and aging in cardiomyocytes; and are involved in macrophage polarization and contribute significantly to cardiac disease development. Cardiac macrophages not only trigger damaging inflammatory responses during atherosclerotic plaque formation, myocardial injury, and heart failure but are also involved in tissue repair, remodeling, and regeneration. In this review, we summarize the key epigenetic modifications that influence macrophage polarization and contribute to the pathophysiology of CVDs, and highlight their potential for the development of advanced epigenetic therapies.
心血管疾病(CVDs)是全球住院和死亡的主要原因,在发展中国家尤为如此。尽管已经开发了多种预防和治疗方法,但CVDs的患病率和死亡率仍在上升,这是全球健康领域令人担忧的趋势。慢性炎症和巨噬细胞浸润是CVDs发生和发展的关键调节因素。最近的数据表明,表观遗传修饰,如DNA甲基化、翻译后组蛋白修饰和RNA修饰,可调节心肌细胞的细胞发育、DNA损伤修复、细胞凋亡、免疫、钙信号传导和衰老;并参与巨噬细胞极化,对心脏病的发展有重要影响。心脏巨噬细胞不仅在动脉粥样硬化斑块形成、心肌损伤和心力衰竭期间引发破坏性炎症反应,还参与组织修复、重塑和再生。在这篇综述中,我们总结了影响巨噬细胞极化并导致CVDs病理生理的关键表观遗传修饰,并强调了它们在先进表观遗传疗法开发中的潜力。