近期，全球肥胖病因导致的流行病和肥胖引发的心血管疾病已成为主要的发病率和死亡率因素之一。这种流行病导致心脏组织中的不良事件始于高密度脂蛋白和低密度脂蛋白（LDL）的分布和代谢模式的改变，导致胆固醇（氧化LDL）在动脉壁上沉积和动脉粥样硬化斑块的生成，随后出现血管痉挛和梗死。随后，肥胖引起的代谢紊乱导致自由基的产生，可能进一步引发促炎症信号和核因子kappa-轻链增强激活的B细胞转录因子，从而诱导γ-干扰素、肿瘤坏死因子-α和可诱导型一氧化氮合酶的产生。这种可怕的心肌病在2型糖尿病患者中可能进一步加重，因此使肥胖糖尿病患者比非糖尿病患者更容易发生心肌梗死（MI）或中风。加速的氧化应激和促炎症反应诱导肥胖糖尿病患者的心肌细胞肥大，随后发生细胞凋亡，导致动脉-血栓形成性血管疾病的进展。褪黑激素作为一种高效的抗氧化和抗炎症的吲哚胺，可以有效抑制脂质过氧化和促炎症反应，从而解决自由基引起的心肌损伤，并保持抗氧化物质库，以维持心血管的完整性。长期的褪黑素治疗可以通过抑制胆固醇的合成和促进胆固醇的降解，维持体重平衡和血清总胆固醇浓度。此外，褪黑素促进巨噬细胞向抗炎状态极化，为恢复期提供适当的保护屏障。因此，褪黑素在维持脂质代谢平衡和阻止动脉粥样硬化斑块破裂方面的保护作用可能是针对管理肥胖引起的急性MI的可能治疗策略。本综述旨在协调褪黑素在缓解肥胖-糖尿病相关引起的不可逆氧化性心血管损伤方面的功效。 © 2022 John Wiley＆Sons A/S。由John Wiley＆Sons Ltd.发布。

In recent days, the hike in obesity-mediated epidemics across the globe and the prevalence of obesity-induced cardiovascular disease has become one of the chief grounds for morbidity and mortality. This epidemic-driven detrimental events in the cardiac tissues start with the altered distribution and metabolism pattern of high-density lipoprotein and low-density lipoprotein (LDL) leading to cholesterol (oxidized LDL) deposition on the arterial wall and atherosclerotic plaque generation, followed by vascular spasms and infarction. Subsequently, obesity-triggered metabolic malfunctions induce free radical generation which may further trigger pro-inflammatory signaling and nuclear factor kappa-light-chain-enhancer of activated B cells transcriptional factor, thus inducing interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase. This terrifying cardiomyopathy can be further aggravated in type 2 diabetes mellitus, thereby making obese diabetic patients prone toward the development of myocardial infarction (MI) or stroke in comparison to their nondiabetic counterparts. The accelerated oxidative stress and pro-inflammatory response induced cardiomyocyte hypertrophy, followed by apoptosis in obese diabetic individuals, causing progression of athero-thrombotic vascular disease. Being an efficient antioxidative and anti-inflammatory indolamine, melatonin effectively inhibits lipid peroxidation, pro-inflammatory reactions, thereby resolving free radical-induced myocardial damages along with maintaining antioxidant reservoir to preserve cardiovascular integrity. Prolonged melatonin treatment maintains balanced body weight and serum total cholesterol concentration by inhibiting cholesterol synthesis and promoting cholesterol catabolism. Additionally, melatonin promotes macrophage polarization toward the anti-inflammatory state, providing a proper shield during the recovery period. Therefore, the protective role of melatonin in maintaining the lipid metabolism homeostasis and blocking the atherosclerotic plaque rupture could be targeted as the possible therapeutic strategy for the management of obesity-induced acute MI. This review aimed at orchestrating the efficacy of melatonin in ameliorating irrevocable oxidative cardiovascular damage induced by the obesity-diabetes correlation.© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.