Understanding cardiomyocyte proliferation: an insight into cell cycle activity.
Cardiomyocyte proliferation and regeneration are key to the functional recovery of myocardial tissue from injury. In the recent years, studies on cardiomyocyte proliferation overturned the traditional belief that adult cardiomyocytes permanently withdraw from the cell cycle activity. Hence, targeting cardiomyocyte proliferation is one of the potential therapeutic strategies for myocardial regeneration and repair. To achieve this, a deep understanding of the fundamental mechanisms involved in cardiomyocyte cell cycle as well as differences between neonatal and adult cardiomyocytes' cell cycle activity is required. This review focuses on the recent progress in understanding of cardiomyocyte cell cycle activity at different life stages viz., gestation, birth, and adulthood. The temporal expression/activities of major cell cycle activators (cyclins and CDKs), inhibitors (p21, p27, p57, p16, and p18), and cell-cycle-associated proteins (Rb, p107, and p130) in cardiomyocytes during gestation and postnatal life are described in this review. The influence of different transcription factors and microRNAs on the expression of cell cycle proteins is demonstrated. This review also deals major pathways (PI3K/AKT, Wnt/β-catenin, and Hippo-YAP) associated with cardiomyocyte cell cycle progression. Furthermore, the postnatal alterations in structure and cellular events responsible for the loss of cell cycle activity are also illustrated.
Center for Developmental Cardiology, Institute of Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China.
Murugavel
M
Ponnusamy
Center for Developmental Cardiology, Institute of Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China. peifengliqd@163.com.
Pei-Feng
PF
Li
Center for Developmental Cardiology, Institute of Translational Medicine, College of Medicine, Qingdao University, Qingdao, 266021, China. wangk696@163.com.
Kun
K
Wang
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D006321:Heart / Q000196:embryology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D014945:Wound Healing
D035683:MicroRNAs
Cardiomyocytes; Cell cycle; Cyclins; MicroRNAs; Signaling pathways; Transcription factors
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