Research Progress on the Role of Pyroptosis in Myocardial Ischemia-Reperfusion Injury

Abstract

Myocardial ischemia-reperfusion injury (MIRI) results in the aggravation of myocardial injury caused by rapid recanalization of the ischemic myocardium. In the past few years, there is a growing interest in investigating the complex pathophysiological mechanism of MIRI for the identification of effective targets and drugs to alleviate MIRI. Currently, pyroptosis, a type of inflammatory programmed death, has received greater attention. It is involved in the MIRI development in combination with other mechanisms of MIRI, such as oxidative stress, calcium overload, necroptosis, and apoptosis, thereby forming an intertwined association between different pathways that affect MIRI by regulating common pathway molecules. This review describes the pyroptosis mechanism in MIRI and its relationship with other mechanisms, and also highlights non-coding RNAs and non-cardiomyocytes as regulators of cardiomyocyte pyroptosis by mediating associated pathways or proteins to participate in the initiation and development of MIRI. The research progress on novel small molecule drugs, clinical drugs, traditional Chinese medicine, etc. for regulating pyroptosis can play a crucial role in effective MIRI alleviation. When compared to research on other mature mechanisms, the research studies on pyroptosis in MIRI are inadequate. Although many related protective drugs have been identified, these drugs generally lack clinical applications. It is necessary to further explore and verify these drugs to expand their applications in clinical setting. Early inhibition of MIRI by targeted regulation of pyroptosis is a key concern that needs to be addressed in future studies.

Mechanism of DYRK1a in myocardial ischemia–reperfusion injury by regulating ferroptosis of cardiomyocytes

“…28 The aforementioned nine programs participate in complex mechanisms underlying the death of cardiomyocytes. 29,30 Among these, ferroptosis is considered a contributor to I/R injury;…”

“…These cell death programs, particularly the regulated forms of cardiomyocyte death, play significant roles in major cardiac syndromes such as MI with reperfusion and heart failure 28 . The aforementioned nine programs participate in complex mechanisms underlying the death of cardiomyocytes 29,30 . Among these, ferroptosis is considered a contributor to I/R injury; hence, targeting ferroptosis may be a promising protective therapy against I/R injury 31 .…”

Research progress on effects of traditional Chinese medicine on myocardial ischemia–reperfusion injury: A review

“…The nature of MIRI in Chinese medicine mainly lies in two aspects of root vacuity and tip repletion, which interact with each other and jointly affect the pathological process of MIRI. Among them, root vacuity refers to a deficiency of qi and insufficient blood circulation and Yin and Yang, while tip repletion refers to phlegm turbidity, cold coagulation, qi stagnation, blood stasis, and other phenomena ( Li et al, 2021 ). The TCM pathogenesis of MIRI includes qi deficiency, blood stasis, and phlegm turbidity.…”

“…Studies have confirmed that most flavonoids have a certain protective effect on the myocardium, and the bioactive components of Huangqin elicit a cardiac protective effect through some channels ( Sun W. et al, 2021 ). Li and Yu’s (2021) study has shown that WG could increase Nrf2 expression and regulate the redox system balance in MIRI rats ( Li et al, 2021 ). Additionally, the expression of HO-1 also increased.…”

Human umbilical cord derived mesenchymal stem cells overexpressing HO‐1 attenuate neural injury and enhance functional recovery by inhibiting inflammation in stroke mice

“…Treating cerebral ischemia is particularly challenging because of the rapid progression of the injury 3 . Inflammatory reactions initiated at the blood–microvessel interface a few hours after the onset of ischemia underlie the transition from ischemic to inflammatory injury 4 . A phenomenon called ischemia–reperfusion injury is often observed once blood flow is restored.…”