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The Role of P53 in Myocardial Ischemia-Reperfusion Injury

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Abstract

Purpose

P53 is one of the key tumor suppressors. In normal cells, p53 is maintained at low levels by the ubiquitination of the ubiquitinated ligase MDM2. In contrast, under stress conditions such as DNA damage and ischemia, the interaction between p53 and MDM2 is blocked and activated by phosphorylation and acetylation, thereby mediating the trans-activation of p53 through its target genes to regulate a variety of cellular responses. Previous studies have shown that the expression of p53 is negligible in normal myocardium, tends to increase in myocardial ischemia and is maximally induced in ischemia-reperfused myocardium, demonstrating a possible key role of p53 in the development of MIRI. In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and describe the therapeutic agents targeting the relevant targets to provide new strategies for the prevention and treatment of MIRI.

Methods

We collected 161 relevant papers mainly from Pubmed and Web of Science (search terms "p53" and "myocardial ischemia-reperfusion injury"). After that, we selected pathway studies related to p53 and classified them according to their contents. We eventually analyzed and summarized them.

Results and conclusion

In this review, we detail and summarize recent studies on the mechanism of action of p53 in MIRI and validate its status as an important intermediate affecting MIRI. On the one hand, p53 is regulated and modified by multiple factors, especially non-coding RNAs; on the other hand, p53 regulates apoptosis, programmed necrosis, autophagy, iron death and oxidative stress in MIRI through multiple pathways. More importantly, several studies have reported medications targeting p53-related therapeutic targets. These medications are expected to be effective options for the alleviation of MIRI, but further safety and clinical studies are needed to convert them into clinical applications.

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Funding

This research was supported by grants from the National Natural Science Foundation of China (82202408，81970722 and 82172160).

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  1. Department of Anesthesiology, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Road, Wuhan, Hubei, 430060, People’s Republic of China

    Xi-zi Zhu, Zhen Qiu, Shao-qing Lei, Yan Leng, Wen-yuan Li & Zhong-yuan Xia

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  1. Xi-zi Zhu
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  2. Zhen Qiu
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  4. Yan Leng
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Conceptualization, XXZ and ZYX; data collection, curation, and original draft preparation, XXZ and ZQ; review and editing, all authors; visualization, XXZ and ZQ; supervision, SQL and ZYX; project administration and funding acquisition, ZYX. All authors read and approved the final manuscript.

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Zhu, Xz., Qiu, Z., Lei, Sq. et al. The Role of P53 in Myocardial Ischemia-Reperfusion Injury. Cardiovasc Drugs Ther (2023). https://doi.org/10.1007/s10557-023-07480-x

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