Chinese Herbal Medicine Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating Endoplasmic Reticulum Stress.

Wu-Lin Liang,Shuo-Feng Zhang,Zhan-Hong Jia,Yong-Hong Wu,Meng-Ru Cai,Shuang Cui,Wen-Hao Cheng,Wen-Jing Ou,Tian-Rui Zhang,Ming-Qian Zhang,Gioacchino Calapai

doi:10.1155/2021/4963346

Abstract

Myocardial ischemia/reperfusion injury is the main cause of increased mortality and disability in cardiovascular diseases. The injury involves many pathological processes, such as oxidative stress, calcium homeostasis imbalance, inflammation, and energy metabolism disorders, and these pathological stimuli can activate endoplasmic reticulum stress. In the early stage of ischemia, endoplasmic reticulum stress alleviates the injury as an adaptive survival response, but the long-term stress on endoplasmic reticulum amplifies oxidative stress, inflammation, and calcium overload to accelerate cell damage and apoptosis. Therefore, regulation of endoplasmic reticulum stress may be a mechanism to improve ischemia/reperfusion injury. Chinese herbal medicine has a long history of clinical application and unique advantages in the treatment of ischemic heart diseases. This review focuses on the effect of Chinese herbal medicine on myocardial ischemia/reperfusion injury from the perspective of regulation of endoplasmic reticulum stress.

Highlights

Myocardial infarction continues to be a leading contributor to deaths globally. e timely recovery of blood perfusion to the ischemic myocardium remains the most effective treatment strategy for myocardial infarction, and successful recovery significantly reduces the morbidity and mortality
endoplasmic reticulum (ER) stress is involved in many pathological processes of cardiovascular diseases (CVDs), and the unfolded protein response (UPR) activated by ER stress plays a key role
E UPR is a defense mechanism that is induced by three pathways, and it protects cardiomyocytes by maintaining ER homeostasis

Summary

Introduction

Myocardial infarction continues to be a leading contributor to deaths globally. e timely recovery of blood perfusion to the ischemic myocardium remains the most effective treatment strategy for myocardial infarction, and successful recovery significantly reduces the morbidity and mortality. Enters the nucleus and binds to the ER stress response element (ESE) in the promoter regions of the UPR target genes to induce the transcription of genes participating in chaperones, protein folding, ERAD, and regulation of metabolism [14]. In chronic or severe ER stress, PERK-mediated phosphorylation of eIF2α promotes the selective translation of several mRNAs, such as those encoding activating transcription factor 4 (ATF4). In the Golgi, ATF6 is hydrolyzed by Site-1 and Site-2 proteases to produce cytoplasmic fragments with transcriptional activity; the processed nuclear ATF6 (ATF6n) enters the nucleus and binds to the ESE in the promoter regions of the UPR target genes to promote the transcription of genes involved in protein folding and degradation, enhancing the folding ability of the ER and restoring the stability of the intracellular environment [25]. During long-term I/R injury, the prosurvival effect of the UPR eventually changes to a proapoptotic effect (Figure 2)

Prosurvival Effect of ER Stress

Conclusions

Findings

Conflicts of Interest