Mechanisms of Cell Death in Heart Disease

Konstantinidis, Klitos; Whelan, Russell S.; Kitsis, Richard N.

doi:10.1161/atvbaha.111.224915

Cited by 327 publications

(299 citation statements)

References 134 publications

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“…1 Traditionally, necrosis is regarded as a passive and unregulated cell death, while apoptosis has long been considered as the sole form of programmed cell death. However, emerging evidences suggest that a proportion of necrosis is regulated by serial signaling events in a controlled and orchestrated manner.…”

mentioning

confidence: 99%

E2F1-regulated miR-30b suppresses Cyclophilin D and protects heart from ischemia/reperfusion injury and necrotic cell death

Wang

Zhou

et al. 2014

Cell Death Differ

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Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Cell death is a hallmark characteristic of various cardiac diseases, including myocardial infarction and heart failure. Emerging evidences suggest that necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. However, the molecular components regulating programmed necrosis in heart remain largely unidentified. Here we report that miR-30b, Cyclophilin D (CypD) and E2F1 constitute an axis that regulates necrosis. The results show that knockdown of CypD attenuated necrosis in the cellular model and also myocardial infarction in the animal model. miR-30b suppresses the translation of CypD and thus inhibits CypD-mediated necrotic cell death in cardiomyocytes. Cardiac-specific miR-30b transgenic mice exhibit reduced necrosis and myocardial infarct size upon ischemia/reperfusion (I/R) injury. Further, we identify that E2F1 transcriptionally represses miR-30b expression. Knockdown of E2F1 in cardiomyocytes inhibits necrotic cell death, and E2F1 knockout mice show reduced necrosis and myocardial infarct size upon I/R. Our present study identifies a novel signaling pathway composed of E2F1, miR-30b and CypD that regulates myocardial necrosis. This discovery will not only provide de novo regulators in the necrotic process but will also shed new light on the effective therapy of myocardial infarction and heart failure.

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mentioning

confidence: 99%

E2F1-regulated miR-30b suppresses Cyclophilin D and protects heart from ischemia/reperfusion injury and necrotic cell death

Wang

Zhou

et al. 2014

Cell Death Differ

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“…Myocardial infarction is generally caused by blood coagulate, that breaks the blood movement to the part of cardiac cells. 20 Treatment of myocardial infarction with clot-breaking medicine procedure is usually done to bring back the blood flow over the clogged blood vessel are commonly done. 21 The injured tissues of the heart in myocardial infarction can also be repaired by the replacement of damaged cells using stem cell therapy in cellular transplantation.…”

Section: Discussionmentioning

confidence: 99%

Combine Effect of 5-Azacytidine and TGF- β in Differentiation of Mesenchymal Stem Cells towards Cardiomyocytes

Shams

Naseer

Hassan

2017

JSRT

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Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Although pharmaceutical therapy and revascularization strategies are able to delay ventricular remodeling, until today no therapeutic strategy is available that might prevent or reverse the process of remodeling and ventricular failure. In the recent past stem cells regenerative therapy has been presented the best tool for treatment of MI. Bone marrow derived mesenchymal stem cells (MSCs) can be differentiated into different types of cells. In the current study, bone marrow derived MSCs were isolated from femur and tibia of Balb C Mice and were cultured in 5-azacytidine and 10ng/μl transforming growth factor (TGF-β) in different groups. The RT-PCR analysis demonstrated that combine treatment of MSCs with 5-azacytidine and TGF-β have high effect on MScs differentiation towards cardiomyocytes as compare to 5-azacytidine and TGF-β alone. The cardiac specific genes GATA 4 and cTnT were highly expressed in the combined 5-azacytidine+TGF-β treated cells, while GAPDH was used as control. The present study is anticipated to put forward valued aspect of differentiation of bone marrow derived MSCs into cardiac cells. This might assist as a means for improved cellular treatment and might enhance the possibility of improved myocardial regeneration.Keywords: myocardial infarction, mscs, tgf-β, gapdh, ace, dnmts Journal of Stem Cell Research & Therapeutics Research ArticleOpen Access Combine effect of 5-azacytidine and tgf-β in differentiation of mesenchymal stem cells towards cardiomyocytes 203Copyright: ©2017 Shams et al.Citation: Shams S, Naseer M, Hassan H. Combine effect of 5-azacytidine and tgf-β in differentiation of mesenchymal stem cells towards cardiomyocytes.

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“…Notably, it has been demonstrated that the deletion of cardiomyocytes ultimately leads to HF (Olivetti et al, 1997). Nearly all types of HF are accompanied by increased cell death, attributed to stresses from circulating neurohormones, inflammation, oxidative stress, or toxins (Konstantinidis et al, 2012;Richter and Kostin, 2015). This leads to the release of growth factors which can result in the formation of fibrosis (Gandhi et al, 2011).…”

Section: Epidemiology and Pathophysiology Of Hfmentioning

confidence: 99%

Roles of SIRT3 in heart failure: from bench to bedside

Liu

Song

et al. 2016

J. Zhejiang Univ. Sci. B

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Heart failure (HF) represents the most common endpoint of most cardiovascular diseases (CVDs) which are the leading causes of death around the world. Despite the advances in treating CVDs, the prevalence of HF continues to increase. It is believed that better results of prognosis are obtained from prevention rather than additional treatment for HF. Therefore, it is reasonable to prevent the development of CVDs or other complications to HF. Most types of HF are attributed to contractile dysfunction, cardiac hypertrophy or remodeling, and ischemic injuries. SIRT3 is a mitochondrial nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase whose substrates vary from metabolic biogenesis-associated proteins to stress-responsive proteins. In recent years, a number of studies have highlighted the cardio-protective role of SIRT3 and, as such, efforts have been made to induce over-expression or increased activity of this protein. In this review, we provide an overview of the roles of SIRT3 in cardiac hypertrophy induced by pressure overload or agonists and cardiomyocytes ischemic injuries. Moreover, we will introduce the application of SIRT3 agonists in the prevention of cardiac hypertrophy and ischemia reperfusion injury.

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Mechanisms of Cell Death in Heart Disease

Cited by 327 publications

References 134 publications

E2F1-regulated miR-30b suppresses Cyclophilin D and protects heart from ischemia/reperfusion injury and necrotic cell death

E2F1-regulated miR-30b suppresses Cyclophilin D and protects heart from ischemia/reperfusion injury and necrotic cell death

Combine Effect of 5-Azacytidine and TGF- β in Differentiation of Mesenchymal Stem Cells towards Cardiomyocytes

Roles of SIRT3 in heart failure: from bench to bedside

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