Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan.
Department of Pharmacology and Physiology, Université de Montréal, Montreal, Quebec, Canada; Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, Quebec, Canada.
Eur J Pharmacol. 2021 Jan 15;891:173765. doi: 10.1016/j.ejphar.2020.173765. Epub 2020 Nov 26.
Peptidylarginine deiminase (PAD) family members have a vital role in maintaining the stability of the extracellular matrix (ECM) during remodelling in several heart diseases. PAD-mediated deamination, or citrullination, has been studied in different physiological and pathological conditions in the body. However, the role of PAD isoforms has not been fully studied in cardiovascular system. Citrullination is a post-translational modification that involves conversion of peptidyl-based arginine to peptidyl-based citrulline by PAD family members in a calcium-dependent manner. Upregulation of PADs have been observed in various cardiovascular diseases, including venous thrombosis, cardiac fibrosis, heart failure, atherosclerosis, coronary heart disease and acute inflammation. In this review, experimental aspects of in vivo and in vitro studies related to the roles PAD isoforms in cardiovascular diseases including mechanisms, pathophysiological and therapeutic properties are discussed. Pharmacological strategies for targeting PAD family proteins in cardiac diseases have not yet been studied. Furthermore, the role played by PAD family members in the remodelling process during the progression of cardiovascular diseases is not fully understood.
肽基精氨酸脱亚氨酶（PAD）家族成员在几种心脏病 remodelling 过程中对维持细胞外基质（ECM）的稳定性起着至关重要的作用。PAD 介导的脱氨作用，或瓜氨酸化，已在体内不同的生理和病理条件下进行了研究。然而，PAD 同工酶在心血管系统中的作用尚未得到充分研究。瓜氨酸化是一种翻译后修饰，涉及 PAD 家族成员以钙依赖性方式将基于肽的精氨酸转化为基于肽的瓜氨酸。在各种心血管疾病中，包括静脉血栓形成、心脏纤维化、心力衰竭、动脉粥样硬化、冠心病和急性炎症，都观察到 PAD 的上调。本综述讨论了与 PAD 同工酶在心血管疾病中的作用相关的体内和体外研究的实验方面，包括机制、病理生理和治疗特性。尚未研究针对心脏疾病中 PAD 家族蛋白的药理学策略。此外，PAD 家族成员在心血管疾病进展过程中的重塑过程中所扮演的角色还不完全清楚。
