University of Wyoming College of Health Sciences, Laramie, WY 82071, USA; Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China.
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China.
Pharmacol Res. 2022 Feb;176:106072. doi: 10.1016/j.phrs.2022.106072. Epub 2022 Jan 8.
Atherosclerosis refers to a unique form of chronic proinflammatory anomaly of the vasculature, presented as rupture-prone or occlusive lesions in arteries. In advanced stages, atherosclerosis leads to the onset and development of multiple cardiovascular diseases with lethal consequences. Inflammatory cytokines in atherosclerotic lesions contribute to the exacerbation of atherosclerosis. Pharmacotherapies targeting dyslipidemia, hypercholesterolemia, and neutralizing inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have displayed proven promises although contradictory results. Moreover, adjuvants such as melatonin, a pluripotent agent with proven anti-inflammatory, anti-oxidative and neuroprotective properties, also display potentials in alleviating cytokine secretion in macrophages through mitophagy activation. Here, we share our perspectives on this concept and present melatonin-based therapeutics as a means to modulate mitophagy in macrophages and, thereby, ameliorate atherosclerosis.
动脉粥样硬化是一种独特的血管慢性炎症异常，表现为动脉易破裂或闭塞性病变。在晚期，动脉粥样硬化会导致多种心血管疾病的发作和发展，从而带来致命的后果。动脉粥样硬化病变中的炎症细胞因子会加剧动脉粥样硬化的发生。针对血脂异常、高胆固醇血症以及中和炎症细胞因子（TNF-α、IL-1β、IL-6、IL-17 和 IL-12/23）的药物治疗已经显示出了一定的疗效，尽管结果存在争议。此外，褪黑素等佐剂作为一种具有多种功能的药物，已被证明具有抗炎、抗氧化和神经保护作用，也显示出通过激活线粒体自噬来减轻巨噬细胞中细胞因子分泌的潜力。在这里，我们分享了我们对这一概念的看法，并提出了基于褪黑素的治疗方法，以调节巨噬细胞中的线粒体自噬，从而改善动脉粥样硬化。
