The regulatory roles of p53 in cardiovascular health and disease
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Cellular and Molecular Life Sciences
REVIEW
The regulatory roles of p53 in cardiovascular health and disease Hongbo Men1,2 · He Cai1 · Quanli Cheng1 · Wenqian Zhou1,2 · Xiang Wang1,2 · Shan Huang1,2 · Yang Zheng1 · Lu Cai2,3 Received: 31 July 2020 / Revised: 22 October 2020 / Accepted: 29 October 2020 © Springer Nature Switzerland AG 2020
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. Keywords p53 · Cardiovascular disease · Apoptosis · Angiogenesis · Metabolism · Cell cycle arrest
Introduction The heart is one of the most important organs of the body that works as a blood pump to provide the body with oxygen and nutrients. Heart health is, therefore, a vital factor contributing to the quality of life and longevity. Cardiovascular disease (CVD) is currently the leading cause of death worldwide. According to the 2020 update of American Heart Association Heart Disease and Stroke Statistics, CVD accounted for approximately 18 million deaths in 2017, and the expenditures for CVD surpassed the medical cost of any * Yang Zheng [email protected] * Lu Cai [email protected] 1
Department of Cardiovascular Disease, First Hospital of Jilin University, Jilin University, Changchun 130021, China
2
Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY 40202, USA
3
Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA
other chronic disease [1]. It is, therefore, urgent to determine the mechanisms underlying heart diseases. In the past three decades, p53 has received increased attention from researchers. A massive amount of evidence has shown that p53 is a tra
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