Department of Medicine, Faculty of Medicine, Montreal Heart Institute (MHI), Université de Montréal, Research Center, 5000 Belanger, St. Montreal, QC, H1T 1C8, Canada.
Mol Biol Rep. 2022 Jun;49(6):5179-5197. doi: 10.1007/s11033-022-07230-6. Epub 2022 Feb 10.
Chronic heart diseases have in common an unresolved inflammatory status. In atherosclerosis, myocarditis, myocardial infarction, or atrial fibrillation, mounting evidence suggests that unresolved inflammation contributes to the chronicity, aggravation, and morbidity of the disease. Following cardiac injury or infection, acute inflammation is a normal and required process to repair damaged tissues or eliminate pathogens and promote restoration of normal functions and structures. However, if acute inflammation is not followed by resolution, a chronic and deleterious inflammatory status may occur, characterized by the persistence of inflammatory biomarkers, promoting aggravation of myocardial pathogenesis, abnormal structural remodeling, development of cardiac fibrosis, and loss of function. Although traditional antiinflammatory strategies, including the use of COX-inhibitors, to inhibit the production of inflammation promotors failed to promote homeostasis, mounting evidence suggests that activation of specific endogenous autacoids may promote resolution and perpetuate cardioprotective effects. The recent discovery of the active mechanism of resolution suggests that proresolving signals and cellular processes may help to terminate inflammation and combat the development of its chronic profile in cardiac diseases. This review discussed (I) the preclinical and clinical evidence of inflammation-resolution in cardiac disorders including atrial fibrillation; (II) how and why many traditional antiinflammatory treatments failed to prevent or cure cardiac inflammation and fibrosis; and (III) whether new therapeutic strategies may interact with the resolution machinery to have cardioprotective effects. RvD D-series resolving, RvE E-series resolving, LXA4 lipoxin A4, MaR1 maresin-1.
慢性心脏疾病都存在未解决的炎症状态。在动脉粥样硬化、心肌炎、心肌梗死或心房颤动中，越来越多的证据表明，未解决的炎症会导致疾病的慢性化、加重和发病。在心脏损伤或感染后，急性炎症是修复受损组织或消除病原体并促进正常功能和结构恢复的正常和必需过程。然而，如果急性炎症后没有得到解决，可能会发生慢性和有害的炎症状态，其特征是炎症生物标志物持续存在，促进心肌发病机制的加重、异常结构重塑、心脏纤维化的发展和功能丧失。尽管包括使用 COX 抑制剂在内的传统抗炎策略旨在抑制炎症促进剂的产生，但未能促进体内平衡，越来越多的证据表明，激活特定的内源性自诱导物可能会促进解决并维持心脏保护作用。解决炎症的新发现机制表明，促解决信号和细胞过程可能有助于终止炎症并对抗其在心脏疾病中的慢性发展。本综述讨论了（I）炎症解决在包括心房颤动在内的心脏疾病中的临床前和临床证据；（II）为什么许多传统的抗炎治疗未能预防或治愈心脏炎症和纤维化；以及（III）新的治疗策略是否可能与解决机制相互作用以产生心脏保护作用。RvD 系列 D 型解决物、RvE 系列 E 型解决物、LXA4 脂氧素 A4、MaR1maresin-1。
