Role of noncoding RNAs in regulation of cardiac cell death and cardiovascular diseases

Pyroptosis is the most recently identified type of regulated cell death with inflammatory response and has characteristics distinct from those of apoptosis or necrosis. Recently, independent studies have reported that small noncoding RNAs termed microRNAs (miRNAs) are involved in the regulation of pyroptosis. Nevertheless, only a handful of empirical data regarding miRNA-dependent regulation of pyroptosis is currently available. This review is aimed to provide a current update on the role of miRNAs in pyroptosis and to offer suggestions for future studies probing miRNAs as a linker connecting pyroptosis to various cardiovascular diseases (CVDs) and their potential as a therapeutic target for preventing excessive cell death of myocardium during CVDs.

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Abstract 26: Fibroblast Growth Factor 21 Prevents Diabetic Cardiomyopathy by Attenuating Cardiac Lipotoxicity via Erk1/2-dependent Signaling Pathway in Mice

Circulation Research ◽

10.1161/res.117.suppl_1.26 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

Yi Tan ◽

Chi Zhang ◽

Xiaoqing Yan ◽

Zhifeng Huang ◽

Junlian Gu ◽

...

Keyword(s):

Cell Death ◽

Type 1 Diabetes ◽

Signaling Pathway ◽

P38 Mapk ◽

Diabetic Cardiomyopathy ◽

Cardiac Cell ◽

Diabetic Mice ◽

Ampk Signaling

The role of FGF21 plays in the development and progression of diabetic cardiomyopathy (DCM) has not been addressed. Here we demonstrated that type 1 diabetes decreased FGF21 levels in the blood, but up-regulated cardiac fgf21 expression about 40 fold at 2 months and 3-1.5 fold at 4 and 6 months after diabetes, which indicated a cardiac specific FGF21 adaptive up-regulation. To define the critical role of FGF21 in DCM, type 1 diabetes was induced in FGF21 knock out (FGF21KO) mice. At 1, 2 and 4 months after diabetes onset, no significant differences between FGF21KO and wild type (WT) diabetic mice in blood glucose and triglyceride levels were observed. But FGF21KO diabetic mice showed earlier and more severe cardiac dysfunction, remodeling and oxidative stress, as well as greater increase in cardiac lipid accumulation than WT diabetic mice. Mechanistically, FGF21 reduced palmitate-induced cardiac cell death, which was accompanied by up-regulation of cardiac Erk1/2, p38 MAPK and AMPK phosphorylation. Inhibition of each kinase with its inhibitor and/ or siRNA revealed that FGF21 prevents palmitate-induced cardiac cell death via up-regulating the Erk1/2-dependent p38 MAPK/AMPK signaling pathway. In vivo administration of FGF21, but not FGF21 plus ERK1/2 inhibitor, to diabetic mice significantly prevented cardiac cell death and reduced inactivation of Erk1/2, p38 MAPK and AMPK, and prevented cardiac remodeling and dysfunction at late-stage. Our results demonstrate that cardiac FGF21 decompensation may contribute to the development of DCM and FGF21 may be a therapeutic target for the treatment of diabetic cardiac damage via activation of Erk1/2-P38 MAPK-AMPK signaling.

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Autophagy in cardiovascular diseases: role of noncoding RNAs

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2020.10.039 ◽

2021 ◽

Vol 23 ◽

pp. 101-118

Author(s):

Jinning Gao ◽

Xiatian Chen ◽

Chan Shan ◽

Yin Wang ◽

Peifeng Li ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Noncoding Rnas

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More on R 56865 - the role of calcium in ischaemic cardiac cell death

Inpharma Weekly ◽

10.2165/00128413-199108100-00016 ◽

1991 ◽

Vol &NA; (810) ◽

pp. 7

Author(s):

&NA;

Keyword(s):

Cell Death ◽

Cardiac Cell ◽

R 56865

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Role of long noncoding RNAs in tumor cell death

Scientia Sinica Vitae ◽

10.1360/ssv-2021-0413 ◽

2021 ◽

Author(s):

ZhengZheng LI ◽

XueFeng LIU

Keyword(s):

Cell Death ◽

Tumor Cell ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Tumor Cell Death

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Implication of Gut Microbiota in Cardiovascular Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5394096 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Wenyi Zhou ◽

Yiyu Cheng ◽

Ping Zhu ◽

M. I. Nasser ◽

Xueyan Zhang ◽

...

Keyword(s):

Cell Death ◽

Cardiovascular Diseases ◽

Programmed Cell Death ◽

Gut Microbiota ◽

Intestinal Flora ◽

Short Chain Fatty Acids ◽

Secondary Bile Acid ◽

Cardiac Disorders ◽

The Relationship

Emerging evidence has identified the association between gut microbiota and various diseases, including cardiovascular diseases (CVDs). Altered intestinal flora composition has been described in detail in CVDs, such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia. In contrast, the importance of fermentation metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acid (BA), has also been implicated in CVD development, prevention, treatment, and prognosis. The potential mechanisms are conventionally thought to involve immune regulation, host energy metabolism, and oxidative stress. However, numerous types of programmed cell death, including apoptosis, autophagy, pyroptosis, ferroptosis, and clockophagy, also serve as a key link in microbiome-host cross talk. In this review, we introduced and summarized the results from recent studies dealing with the relationship between gut microbiota and cardiac disorders, highlighting the role of programmed cell death. We hope to shed light on microbiota-targeted therapeutic strategies in CVD management.

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Bcl-2 family members and apoptosis, taken to heart

AJP Cell Physiology ◽

10.1152/ajpcell.00229.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. C45-C51 ◽

Cited By ~ 189

Author(s):

Åsa B. Gustafsson ◽

Roberta A. Gottlieb

Keyword(s):

Heart Failure ◽

Cell Death ◽

Heart Disease ◽

Cardiovascular Diseases ◽

Family Members ◽

Mitochondrial Pathway ◽

Myocardial Cells ◽

Antiapoptotic Proteins ◽

Cell Death Program

Loss of myocardial cells via apoptosis has been observed in many cardiovascular diseases and has been shown to contribute to the initiation and progression of heart failure. The Bcl-2 family members are important regulators of the mitochondrial pathway of apoptosis. These proteins decide whether the mitochondria should initiate the cell death program and release proapoptotic factors such as cytochrome c. The Bcl-2 proteins consist of anti- and proapoptotic members and play a key role in regulating apoptosis in the myocardium. The antiapoptotic proteins have been demonstrated to protect against various cardiac pathologies, whereas the antiapoptotic proteins have been reported to contribute to heart disease. This review summarizes the current understanding of the role of Bcl-2 proteins in the heart.

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SARS-CoV-2, Cardiovascular Diseases and Noncoding RNAs: A Connected Triad

International Journal of Molecular Sciences ◽

10.3390/ijms222212243 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12243

Author(s):

Lucia Natarelli ◽

Fabio Virgili ◽

Christian Weber

Keyword(s):

Gene Expression ◽

Cardiovascular Diseases ◽

Regulation Of Gene Expression ◽

Noncoding Rnas ◽

Adverse Outcomes ◽

Rna Molecules ◽

Clinical Level ◽

Important Target ◽

Stable Conditions

Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is characterized by important respiratory impairments frequently associated with severe cardiovascular damages. Moreover, patients with pre-existing comorbidity for cardiovascular diseases (CVD) often present a dramatic increase in inflammatory cytokines release, which increases the severity and adverse outcomes of the infection and, finally, mortality risk. Despite this evident association at the clinical level, the mechanisms linking CVD and COVID-19 are still blurry and unresolved. Noncoding RNAs (ncRNAs) are functional RNA molecules transcribed from DNA but usually not translated into proteins. They play an important role in the regulation of gene expression, either in relatively stable conditions or as a response to different stimuli, including viral infection, and are therefore considered a possible important target in the design of specific drugs. In this review, we introduce known associations and interactions between COVID-19 and CVD, discussing the role of ncRNAs within SARS-CoV-2 infection from the perspective of the development of efficient pharmacological tools to treat COVID-19 patients and taking into account the equally dramatic associated consequences, such as those affecting the cardiovascular system.

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Ferroptosis Is a Potential Novel Diagnostic and Therapeutic Target for Patients With Cardiomyopathy

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.649045 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhenyu Zhai ◽

Pengtao Zou ◽

Fuxiang Liu ◽

Zirong Xia ◽

Juxiang Li

Keyword(s):

Cell Death ◽

Cardiovascular Diseases ◽

Animal Models ◽

Therapeutic Target ◽

Myocardial Injury ◽

Iron Chelators ◽

Myocardial Cells ◽

Cell Death Pathway ◽

Close Relationship

Cardiomyocyte death is a fundamental progress in cardiomyopathy. However, the mechanism of triggering the death of myocardial cells remains unclear. Ferroptosis, which is the nonapoptotic, iron-dependent, and peroxidation-driven programmed cell death pathway, that is abundant and readily accessible, was not discovered until recently with a pharmacological approach. New researches have demonstrated the close relationship between ferroptosis and the development of many cardiovascular diseases, and several ferroptosis inhibitors, iron chelators, and small antioxidant molecules can relieve myocardial injury by blocking the ferroptosis pathways. Notably, ferroptosis is gradually being considered as an important cell death mechanism in the animal models with multiple cardiomyopathies. In this review, we will discuss the mechanism of ferroptosis and the important role of ferroptosis in cardiomyopathy with a special emphasis on the value of ferroptosis as a potential novel diagnostic and therapeutic target for patients suffering from cardiomyopathy in the future.

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