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The regulatory roles of p53 in cardiovascular health and disease

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Abstract

Cardiovascular disease (CVD) remains the leading cause of mortality globally, so further investigation is required to identify its underlying mechanisms and potential targets for its prevention. The transcription factor p53 functions as a gatekeeper, regulating a myriad of genes to maintain normal cell functions. It has received a great deal of research attention as a tumor suppressor. In the past three decades, evidence has also shown a regulatory role for p53 in the heart. Basal p53 is essential for embryonic cardiac development; it is also necessary to maintain normal heart architecture and physiological function. In pathological cardiovascular circumstances, p53 expression is elevated in both patient samples and animal models. Elevated p53 plays a regulatory role via anti-angiogenesis, pro-programmed cell death, metabolism regulation, and cell cycle arrest regulation. This largely promotes the development of CVDs, particularly cardiac remodeling in the infarcted heart, hypertrophic cardiomyopathy, dilated cardiomyopathy, and diabetic cardiomyopathy. Roles for p53 have also been found in atherosclerosis and chemotherapy-induced cardiotoxicity. However, it has different roles in cardiomyocytes and non-myocytes, even in the same model. In this review, we describe the different effects of p53 in cardiovascular physiological and pathological conditions, in addition to potential CVD therapies targeting p53.

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Acknowledgements

The authors are indebted to Editage (www.editage.cn) for the English writing and editing.

Funding

This work was supported in part by the National Key R&D Program of China (2016YFC0900903 to Yang Zheng). All personnel expenses and partial research-related expenses for Hongbo Men, Wenqian Zhou, Xiang Wang, and Shan Huang when they worked in the University of Louisville (11/2018–3/2021) were provided by the First Hospital of Jilin University, Changchun, China under the agreement of U.S-China Pediatric Research Exchange Training Program.

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Authors and Affiliations

  1. Department of Cardiovascular Disease, First Hospital of Jilin University, Jilin University, Changchun, 130021, China

    Hongbo Men, He Cai, Quanli Cheng, Wenqian Zhou, Xiang Wang, Shan Huang & Yang Zheng

  2. Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY, 40202, USA

    Hongbo Men, Wenqian Zhou, Xiang Wang, Shan Huang & Lu Cai

  3. Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, 40202, USA

    Lu Cai

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  1. Hongbo Men
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  2. He Cai
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  3. Quanli Cheng
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  4. Wenqian Zhou
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  5. Xiang Wang
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  6. Shan Huang
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  7. Yang Zheng
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  8. Lu Cai
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Contributions

HM: Conceptualization and Writing—Original draft preparation. HC, QC, WZ, XW, and SH: Literature searching and summary and Writing—Original draft preparation. YZ: Conceptualization, Reviewing and Editing, and Funding acquisition. LC: Conceptualization, Reviewing, and Editing.

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Correspondence to Yang Zheng or Lu Cai.

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Men, H., Cai, H., Cheng, Q. et al. The regulatory roles of p53 in cardiovascular health and disease. Cell. Mol. Life Sci. 78, 2001–2018 (2021). https://doi.org/10.1007/s00018-020-03694-6

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  • DOI: https://doi.org/10.1007/s00018-020-03694-6

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