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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. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptors (PPARs) play vital roles in cardiovascular pathophysiology, such as energy balance, cell proliferation/apoptosis, inflammatory response, and adipocyte differentiation. These vital roles make PPARs potential targets for therapeutic prevention of cardiovascular diseases (CVDs). Emerging evidence indicates that the crosstalk of microRNAs (miRNAs) and PPARs contributes greatly to CVD pathogenesis. PPARs are inhibited by miRNAs at posttranscriptional mechanisms in the progress of pulmonary hypertension and vascular dysfunction involving cell proliferation/apoptosis, communication, and normal function of endothelial cells and vascular smooth muscle cells. In the development of atherosclerosis and stroke, the activation of PPARs could change the transcripts of target miRNA through miRNA signalling. Furthermore, the mutual regulation of PPARs and miRNAs involves cell proliferation/apoptosis, cardiac remodeling, and dysfunction in heart diseases. In addition, obesity, an important cardiovascular risk, is modulated by the regulatory axis of PPARs/miRNAs, including adipogenesis, adipocyte dysfunction, insulin resistance, and macrophage polarization in adipose tissue. In this review, the crosstalk of PPARs and miRNAs and their emerging regulatory roles are summarized in the context of CVDs and risks. This provides an understanding of the underlying mechanism of the biological process related to CVD pathophysiology involving the interaction of PPARs and miRNAs and will lead to the development of PPARs/miRNAs as effective anti-CVD medications. [ABSTRACT FROM AUTHOR]

Necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. MicroRNAs (miRNAs) have emerged as key gene regulators in many diseases. However, how miRNAs contribute to programmed necrosis is poorly defined. Here we report that miR-2861 and adenine nucleotide translocase 1 (ANT1) constitute an axis that regulates necrotic cell death in the heart. Our results show that ANT1 inhibits H 2 O 2 -induced cardiomyocytes necrosis. ANT1 also antagonizes myocardial necrosis in a mouse ischemia/reperfusion (I/R) model. We further demonstrate that miR-2861 directly binds to the coding sequence of ANT1 and suppresses the expression of ANT1 mRNA and protein. MiR-2861 induces necrotic cell death. In contrast, knockdown of miR-2861 attenuates H 2 O 2 -induced necrosis in cardiomyocytes. Also, miR-2861 knockdown protects heart from I/R injury and necrotic cell death in vivo. MiR-2861 regulates necrosis and myocardial infarction through targeting ANT1. Collectively, these data identify miR-2861 and ANT1 as two novel regulators of cardiomyocyte necrosis and myocardial infarction, and suggest potential therapeutic targets in treatment of cardiac diseases. [ABSTRACT FROM AUTHOR]

Abstract: Cardiac hypertrophic program is a chronic, complex process, and occurs in response to long-term increases of hemodynamic load related to a variety of pathophysiological conditions. Mitochondria, known as “the cellular power plants”, occupy about one‐third of cardiomyocyte volume and supply roughly 90% of the adenosine triphosphate (ATP). Impairment of energy metabolism has been regarded as one of the main pathogenesis of cardiac hypertrophy. Thus, we summarize here the molecular events of mitochondrial adaptations, including the mitochondrial genesis, ATP generation, ROS signaling and Ca2+ homeostasis in cardiac hypertrophy, expecting that this effort will shed new light on understanding the maladaptive cardiac remodeling. [Copyright &y& Elsevier]