Mitochondrial disorder and treatment of ischemic cardiomyopathy: Potential and advantages of Chinese herbal medicine

Mitochondrial dysfunction is the main cause of damage to the pathological mechanism of ischemic cardiomy-opathy. In addition, mitochondrial dysfunction can also affect the homeostasis of cardiomyocytes or endothelial cell dysfunction, leading to a vicious cycle of mitochondrial oxidative stress. And mitochondrial dysfunction is also an important pathological basis for ischemic cardiomyopathy and reperfusion injury after myocardial infarction or end-stage coronary heart disease. Therefore, mitochondria can be used as therapeutic targets against myocardial ischemia injury, and the regulation of mitochondrial morphology, function and structure is a key and important way of targeting mitochondrial quality control therapeutic mechanisms. Mitochondrial quality control includes mechanisms such as mitophagy, mitochondrial dynamics (mitochondrial fusion/fission), mitochondrial biosynthesis, and mitochondrial unfolded protein responses. Among them, the increase of mito-chondrial fragmentation caused by mitochondrial pathological fission is the initial factor. The protective mito-chondrial fusion can strengthen the interaction and synthesis of paired mitochondria and promote mitochondrial biosynthesis. In ischemia or hypoxia, pathological mitochondrial fission can promote the formation of mito-chondrial fragments, fragmented mitochondria can lead to damaged mitochondrial DNA production, which can lead to mitochondrial biosynthesis dysfunction, insufficient mitochondrial ATP production, and mitochondrial ROS. Burst growth or loss of mitochondrial membrane potential. This eventually leads to the accumulation of damaged mitochondria. Then, under the leadership of mitophagy, damaged mitochondria can complete the mitochondrial degradation process through mitophagy, and transport the morphologically and structurally damaged mitochondria to lysosomes for degradation. But once the pathological mitochondrial fission increases, the damaged mitochondria increases, which may activate the pathway of cardiomyocyte death. Although lab-oratory studies have found that a variety of mitochondrial-targeted drugs can reduce myocardial ischemia and protect cardiomyocytes, there are still few drugs that have successfully passed clinical trials. In this review, we describe the role of MQS in ischemia/hypoxia-induced cardiomyocyte physiopathology and elucidate the rele-vant mechanisms of mitochondrial dysfunction in ischemic cardiomyopathy. In addition, we also further explained the advantages of natural products in improving mitochondrial dysfunction and protecting myocardial cells from the perspective of pharmacological mechanism, and explained its related mechanisms. Potential tar-geted therapies that can be used to improve MQS under ischemia/hypoxia are discussed, aiming to accelerate the development of cardioprotective drugs targeting mitochondrial dysfunction.

Automated summary

Mitochondrial dysfunction is the main cause of damage in ischemic cardiomyopathy, and it can also affect the homeostasis of cardiomyocytes and endothelial cell function, leading to a vicious cycle of oxidative stress. Regulating mitochondrial morphology, function, and structure is a key way to target mitochondrial quality control mechanisms. This review discusses the role of mitochondrial quality control in ischemia/hypoxia-induced cardiomyocyte pathophysiology and explores potential targeted therapies for improving mitochondrial dysfunction.