The Heart: Mostly Postmitotic or Mostly Premitotic? Myocyte Cell Cycle, Senescence, and Quiescence

Siddiqi, Sailay; Sussman, Mark A.

doi:10.1016/j.cjca.2014.08.014

Cited by 21 publications

(20 citation statements)

References 92 publications

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“…In particular, birth itself triggers innumerable molecular changes as the body transitions from receiving all oxygen and nutrients from the placenta to breathing and eating independently. It is this window of time that cardiomyocytes transition from a proliferative state to a quiescent state [10,11].…”

Section: Introductionmentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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Current methods to differentiate cardiomyocytes from human pluripotent stem cells (PSCs) inadequately recapitulate complete development and result in PSC-derived cardiomyocytes (PSC-CMs) with an immature or fetal-like phenotype. Embryonic and fetal development are highly dynamic periods during which the developing embryo or fetus is exposed to changing nutrient, oxygen, and hormone levels until birth. It is becoming increasingly apparent that these metabolic changes initiate developmental processes to mature cardiomyocytes. Mitochondria are central to these changes, responding to these metabolic changes and transitioning from small, fragmented mitochondria to large organelles capable of producing enough ATP to support the contractile function of the heart. These changes in mitochondria may not simply be a response to cardiomyocyte maturation; the metabolic signals that occur throughout development may actually be central to the maturation process in cardiomyocytes. Here, we review methods to enhance maturation of PSC-CMs and highlight evidence from development indicating the key roles that mitochondria play during cardiomyocyte maturation. We evaluate metabolic transitions that occur during development and how these affect molecular nutrient sensors, discuss how regulation of nutrient sensing pathways affect mitochondrial dynamics and function, and explore how changes in mitochondrial function can affect metabolite production, the cell cycle, and epigenetics to influence maturation of cardiomyocytes.

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Section: Introductionmentioning

confidence: 99%

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Garbern

Lee

2021

Stem Cell Res Ther

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“…It is reported that hypertrophic growth is related to upregulation of G1 cyclin or cyclin-dependent kinases, and that postmitotic cardiac myocytes reenter the cell cycle for proliferative growth (15 , 22 , 23) . To assess how the cell cycle is regulated by cholesterol-induced hypertrophy and reversed by proteasome inhibitors, H9c2 cells were analyzed by flow cytometry assay after treatment with 5 μg/ml cholesterol in the presence or absence of 5 or 50 nM Bortezomib or 5 or 50 nM MG132 for 24 h, followed by staining with propidium iodide.…”

Section: Resultsmentioning

confidence: 99%

Proteasome inhibitors attenuated cholesterol-induced cardiac hypertrophy in H9c2 cells

et al. 2016

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The Ubiquitin proteasome system (UPS) plays roles in protein degradation, cell cycle control, and growth and inflammatory cell signaling. Dysfunction of UPS in cardiac diseases has been seen in many studies. Cholesterol acts as an inducer of cardiac hypertrophy. In this study, the effect of proteasome inhibitors on the cholesterol-induced hypertrophic growth in H9c2 cells is examined in order to observe whether UPS is involved in cardiac hypertrophy. The treatment of proteasome inhibitors MG132 and Bortezomib markedly reduced cellular surface area and mRNA expression of β-MHC in cholesterol-induced cardiac hypertrophy. In addition, activated AKT and ERK were significantly attenuated by MG132 and Bortezomib in cholesterol-induced cardiac hypertrophy. We demonstrated that cholesterol-induced cardiac hypertrophy was suppressed by proteasome inhibitors. Thus, regulatory mechanism of cholesterol-induced cardiac hypertrophy by proteasome inhibitors may provide a new therapeutic strategy to prevent the progression of heart failure. [BMB Reports 2016; 49(5): 270-275]

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“…Tumor suppressor p53 can facilitate cell cycle arrest and senescence program in cells in response to stress [54]. The high expressions of p16 and p53 hamper the resuming cell cycle progression for a senescent cell [55]. Myocyte senescence is associated with oxidative stress, chronic adrenergic signaling, renin-angiotensin-aldosterone signaling (RAAS) and mTORC pathway [55].…”

Section: Discussionmentioning

confidence: 99%

“…The high expressions of p16 and p53 hamper the resuming cell cycle progression for a senescent cell [55]. Myocyte senescence is associated with oxidative stress, chronic adrenergic signaling, renin-angiotensin-aldosterone signaling (RAAS) and mTORC pathway [55]. The mitochondrial functional impairment induces oxidative stress, serves as a primary inciting stimulus for transition into senescence.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Prevents Cardiac Remodeling in the Apolipoprotein E-Deficient Mice by Regulating Cardiac Homeostasis and Oxidative Stress

Ding²,

et al. 2017

Cell Physiol Biochem

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Background: Hypercholesterolemia is a risk factor for the development of cardiac hypertrophy. Astragaloside IV (AST-IV) possesses cardiovascular protective properties. We hypothesize that AST-IV prevents cardiac remodeling with hypercholesterolemia via modulating tissue homeostasis and alleviating oxidative stress. Methods: The ApoE^-/- mice were treated with AST-IV at 1 or 10 mg/kg for 8 weeks. The blood lipids tests, echocardiography, and TUNEL were performed. The mRNA expression profile was detected by real-time PCR. The myocytes size and number, and the expressions of proliferation (ki67), senescence (p16^INK4a), oxidant (NADPH oxidase 4, NOX4) and antioxidant (superoxide dismutase, SOD) were observed by immunofluorescence staining. Results: Neither 1 mg/kg nor 10 mg/kg AST-IV treatment could decrease blood lipids in ApoE^-/- mice. However, the decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS) in ApoE^–/– mice were significantly improved after AST-IV treatment. The cardiac collagen volume fraction declined nearly in half after AST-IV treatment. The enlarged myocyte size was suppressed, and myocyte number was recovered, and the alterations of genes expressions linked to cell cycle, proliferation, senescence, p53-apoptosis pathway and oxidant-antioxidants in the hearts of ApoE^-/- mice were reversed after AST-IV treatment. The decreased ki67 and increased p16^INK4a in the hearts of ApoE^-/- mice were recovered after AST-IV treatment. The percentages of apoptotic myocytes and NOX4-positive cells in AST-IV treated mice were decreased, which were consistent with the gene expressions. Conclusion: AST-IV treatment could prevent cardiac remodeling and recover the impaired ventricular function induced by hypercholesterolemia. The beneficial effect of AST-IV might partly be through regulating cardiac homeostasis and anti-oxidative stress.

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The Heart: Mostly Postmitotic or Mostly Premitotic? Myocyte Cell Cycle, Senescence, and Quiescence

Cited by 21 publications

References 92 publications

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes

Proteasome inhibitors attenuated cholesterol-induced cardiac hypertrophy in H9c2 cells

Astragaloside IV Prevents Cardiac Remodeling in the Apolipoprotein E-Deficient Mice by Regulating Cardiac Homeostasis and Oxidative Stress

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