National Research Mordovia State University, Bolshevitskaya Street, 68, Saransk, 430005, Mordovia Republic, Russia.
Cardiovasc Hematol Disord Drug Targets. 2023;23(1):2-10. doi: 10.2174/1871529X23666230503123612.
Myocardial infarction and its sequalae remain the leading cause of death worldwide. Myocardial infarction (MI) survivors continue to live a poor quality of life due to extinguished heart failure. The post-MI period involves several changes at the cellular and subcellular levels, of which autophagy dysfunction. Autophagy is involved in the regulation of post-MI changes. Physiologically, autophagy preserves intracellular homeostasis by regulating energy expenditure and sources. Furthermore, dysregulated autophagy is considered the hallmark of the post-MI pathophysiological changes, which leads to the known short and long post-MI reperfusion injury sequalae. Autophagy induction strengthens self-defense mechanisms of protection against energy deprivation through economic energy sources and uses alternative sources of energy through the degradation of intracellular components of the cardiomyocyte. The protective mechanism against post-MI injury includes the enhancement of autophagy combined with hypothermia, which induces autophagy. However, several factors regulate autophagy, including starvation, nicotinamide adenine dinucleotide (NAD+), Sirtuins, other natural foods and pharmacological agents. Autophagy dysregulation involves genetics, epigenetics, transcription factors, small noncoding RNAs, small molecules, and special microenvironment. Autophagy therapeutic effects are signaling pathway-dependent and MI stage dependent. The paper covers recent advances in the molecular physiopathology of autophagy in post-MI injury and its potential target as a future therapeutic strategy.
心肌梗死及其后遗症仍然是全球范围内导致死亡的主要原因。由于心力衰竭而熄灭，心肌梗死 (MI) 幸存者继续生活在较差的生活质量中。MI 后时期涉及细胞和亚细胞水平的几个变化，其中自噬功能障碍。自噬参与调节 MI 后的变化。在生理上，自噬通过调节能量消耗和来源来维持细胞内的稳态。此外，失调的自噬被认为是 MI 后病理生理变化的标志，这导致了已知的 MI 后再灌注损伤后遗症的短期和长期。自噬诱导通过经济能源和通过降解心肌细胞的细胞内成分利用替代能源来增强对能量剥夺的自我防御机制。针对 MI 损伤的保护机制包括增强自噬与低温相结合，这会诱导自噬。然而，有几个因素调节自噬，包括饥饿、烟酰胺腺嘌呤二核苷酸 (NAD+)、Sirtuins、其他天然食品和药理学制剂。自噬失调涉及遗传、表观遗传、转录因子、小非编码 RNA、小分子和特殊微环境。自噬的治疗效果依赖于信号通路和 MI 阶段。本文涵盖了自噬在 MI 后损伤中的分子病理生理学及其作为未来治疗策略的潜在靶点的最新进展。
