scholarly journals Mending a broken heart: the role of mitophagy in cardioprotection

2015 ◽  
Vol 308 (3) ◽  
pp. H183-H192 ◽  
Author(s):  
Alexandra G. Moyzis ◽  
Junichi Sadoshima ◽  
Åsa B. Gustafsson
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Cellular Processes ◽  
Differentiated Cells ◽  
Calcium Storage ◽  
Response To Stress ◽  
Metabolite Synthesis ◽  
Energy Dependent

The heart is highly energy dependent with most of its energy provided by mitochondrial oxidative phosphorylation. Mitochondria also play a role in many other essential cellular processes including metabolite synthesis and calcium storage. Therefore, maintaining a functional population of mitochondria is critical for cardiac function. Efficient degradation and replacement of dysfunctional mitochondria ensures cell survival, particularly in terminally differentiated cells such as cardiac myocytes. Mitochondria are eliminated via mitochondrial autophagy or mitophagy. In the heart, mitophagy is an essential housekeeping process and required for cardiac homeostasis. Reduced autophagy and accumulation of impaired mitochondria have been linked to progression of heart failure and aging. In this review, we discuss the pathways that regulate mitophagy in cells and highlight the cardioprotective role of mitophagy in response to stress and aging. We also discuss the therapeutic potential of targeting mitophagy and directions for future investigation.

Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

scholarly journals Autophagy is activated in the ovarian tissue of polycystic ovary syndrome

Reproduction ◽  
2018 ◽  
Vol 155 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Da Li ◽  
Yue You ◽  
Fang-Fang Bi ◽  
Tie-Ning Zhang ◽  
Jiao Jiao ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Potential Role ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Ovary Syndrome ◽  
Cellular Processes ◽  
Transmission Electron ◽  
Wide Range ◽  
Response To Stress

The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased. In addition, the ratio of LC3-II/LC3-I was markedly elevated in human PCOS ovarian tissue compared with normal ovarian tissue. Real-time PCR arrays indicated that 7 and 34 autophagy-related genes were down- and up-regulated in human PCOS , Signal-Net, and regression analysis suggested that there are a wide range of interactions among these 41 genes, and a potential network based on EGFR, ERBB2, FOXO1, MAPK1, NFKB1, IGF1, TP53 and MAPK9 may be responsible for autophagy activation in PCOS. Systematic functional analysis of 41 differential autophagy-related genes indicated that these genes are highly involved in specific cellular processes such as response to stress and stimulus, and are linked to four significant pathways, including the insulin, ERBB, mTOR signaling pathways and protein processing in the endoplasmic reticulum. This study provides evidence for a potential role of autophagy disorders in PCOS in which autophagy may be an important molecular event in the pathogenesis of PCOS.

scholarly journals The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 166 ◽  
Author(s):  
Martha Wium ◽  
Juliano Paccez ◽  
Luiz Zerbini
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Tyrosine Kinases ◽  
Therapeutic Potential ◽  
Cellular Processes ◽  
Tam Receptors ◽  
Different Types ◽  
Extracellular Environment ◽  
Migration And Development

Receptor tyrosine kinases (RTKs) regulate cellular processes by converting signals from the extracellular environment to the cytoplasm and nucleus. Tyro3, Axl, and Mer (TAM) receptors form an RTK family that plays an intricate role in tissue maintenance, phagocytosis, and inflammation as well as cell proliferation, survival, migration, and development. Defects in TAM signaling are associated with numerous autoimmune diseases and different types of cancers. Here, we review the structure of TAM receptors, their ligands, and their biological functions. We discuss the role of TAM receptors and soluble circulating TAM receptors in the autoimmune diseases systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Lastly, we discuss the effect of TAM receptor deregulation in cancer and explore the therapeutic potential of TAM receptors in the treatment of diseases.

Role of the Epigenome in Heart Failure

2020 ◽  
Vol 100 (4) ◽  
pp. 1753-1777 ◽  
Author(s):  
Roberto Papait ◽  
Simone Serio ◽  
Gianluigi Condorelli
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Epigenetic Modification ◽  
Heart Function ◽  
Histone Deacetylation ◽  
Cardiac Phenotype ◽  
Different Types ◽  
Response To Stress ◽  
Histone Methylation And Acetylation

Gene expression is needed for the maintenance of heart function under normal conditions and in response to stress. Each cell type of the heart has a specific program controlling transcription. Different types of stress induce modifications of these programs and, if prolonged, can lead to altered cardiac phenotype and, eventually, to heart failure. The transcriptional status of a gene is regulated by the epigenome, a complex network of DNA and histone modifications. Until a few years ago, our understanding of the role of the epigenome in heart disease was limited to that played by histone deacetylation. But over the last decade, the consequences for the maintenance of homeostasis in the heart and for the development of cardiac hypertrophy of a number of other modifications, including DNA methylation and hydroxymethylation, histone methylation and acetylation, and changes in chromatin architecture, have become better understood. Indeed, it is now clear that many levels of regulation contribute to defining the epigenetic landscape required for correct cardiomyocyte function, and that their perturbation is responsible for cardiac hypertrophy and fibrosis. Here, we review these aspects and draw a picture of what epigenetic modification may imply at the therapeutic level for heart failure.

scholarly journals Long Noncoding RNA SOX2-OT Exacerbates Hypoxia-Induced Cardiomyocytes Injury by Regulating miR-27a-3p/TGFβR1 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Guang Yang ◽  
Chunsheng Lin
Keyword(s):  
Heart Failure ◽  
Cell Apoptosis ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Heart Diseases ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cellular Processes ◽  
Wide Range

Background. Myocardial infarction (MI) was a severe cardiovascular disease resulted from acute, persistent hypoxia, or ischemia condition. Additionally, MI generally led to heart failure, even sudden death. A multitude of research studies proposed that long noncoding RNAs (lncRNAs) frequently participated in the regulation of heart diseases. The specific function and molecular mechanism of SOX2-OT in MI remained unclear. Aim of the Study. The current research was aimed to explore the role of SOX2-OT in MI. Methods. Bioinformatics analysis (DIANA tools and Targetscan) and a wide range of experiments (CCK-8, flow cytometry, RT-qPCR, luciferase reporter, RIP, caspase-3 activity, trans-well, and western blot assays) were adopted to investigate the function and mechanism of SOX2-OT. Results. We discovered that hypoxia treatment decreased cell viability but increased cell apoptosis. Besides, lncRNA SOX2-OT expression was upregulated in hypoxic HCMs. Hereafter, we confirmed that SOX2-OT could negatively regulate miR-27a-3p levels by directly binding with miR-27a-3p, and miR-27a-3p also could negatively regulate SOX2-OT levels. Furthermore, knockdown of SOX2-OT promoted cell proliferation, migration, and invasion, but limited cell apoptosis. However, these effects were reversed by anti-miR-27a-5p. Besides, we verified that miR-27a-3p binding with the 3′UTR of TGFBR1 and SOX2-OT regulated TGFβR1 level by collaborating with miR-27a-3p in HCMs. Eventually, rescue assays validated that the influence of SOX2-OT silence or miR-27a-3p overexpression on cellular processes in cardiomyocytes injury was counteracted by TGFBR1 overexpression. Conclusions. Long noncoding RNA SOX2-OT exacerbated hypoxia-induced cardiomyocytes injury by regulating miR-27a-3p/TGFβR1 axis, which may provide a novel insight for heart failure treatment.

Abstract 414: Putative Role of MicroRNA-143 in Modulating Natriuretic Peptide Signaling via Down-regulation of the Expression of Natriuretic Peptide Receptor 3

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Juan Wang ◽  
Lee L Wong ◽  
Arthur M Richards ◽  
Yei-Tsung Chen
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Natriuretic Peptide ◽  
Therapeutic Potential ◽  
Cardiac Cells ◽  
Luciferase Reporter ◽  
Natriuretic Peptide Receptor ◽  
Down Regulation ◽  
Peptide Receptor

Cardiac natriuretic peptides (NPs) play important roles in the regulation of intravascular blood volume and vascular tone. Among other clearance mechanisms, bio-active circulating NPs are removed by the clearance receptor, Natriuretic Peptide Receptor 3 (NPR3). We hypothesized that the level of NPR3 could be modulated by microRNAs (miRNAs) resulting in changes in the bioactivity of NPs. We have previously reported a cluster of miRNAs potentially regulating NPR3 expression. To extend these findings, expression of the microRNAs concerned was examined in multiple platforms, including plasma from a clinical heart failure cohort, in the rat myocardial infarction model, and in a human cardiac derived cell line subjected to hypoxic challenge. Results: miR-143 was up-regulated in peripheral blood in heart failure patients compared with controls. The binding of miR-143 to the 3’UTR of NPR3 m RNA was verified by luciferase reporter assay. Antagomir-based silencing of miR-143 enhanced NPR3 expression in human derived cardiac cells. Elevation of miR-143 and down-regulation of NPR3 levels were observed in hypoxia treated cells and in the myocardium from the rat myocardial infarction model. Taken together, these findings suggest miR-143 may be involved in the down-regulation of NPR3 which in turn may provide more cardiac protective bioactivity from NPs in heart failure, myocardial hypoxic stress and in myocardial infarction. In summary, NPR3 is negatively regulated by miR-143, pointing to the therapeutic potential of miR-143 to beneficially enhance NP responses.

The Role of Mineralocorticoid Receptor Antagonists in the Management of Heart Failure with Preserved Ejection Fraction

2019 ◽  
Vol 24 (46) ◽  
pp. 5525-5527 ◽  
Author(s):  
Achilleas Papagiannis ◽  
Stelina Alkagiet ◽  
Konstantinos Tziomalos
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mineralocorticoid Receptor ◽  
Therapeutic Potential ◽  
Preserved Ejection Fraction ◽  
Mineralocorticoid Receptor Antagonists ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Definition Of

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with increased risk for hospitalization and all-cause mortality. Currently, there is no established treatment to improve the survival of these patients. Aldosterone appears to play a role in the pathogenesis of HFpEF. Objective: To discuss the findings of studies that evaluated the effects of mineralocorticoid receptor (MR) antagonists on the outcome of patients with HFpEF. Methods: PubMed was searched for relevant papers. References of retrieved articles were also evaluated for pertinent material. Results: Accumulating data suggest that MR antagonists might be useful in the management of patients with HFpEF. However, existing evidence is limited and conflicting. Conclusions: More studies are needed to clearly define the therapeutic potential of MR antagonists in HFpEF. Given the heterogeneity of this disease and the low specificity of the criteria used for its diagnosis, it is also important to improve the definition of HFpEF and include appropriately selected patients in these studies.

scholarly journals Emerging role of hydrogen sulfide-microRNA crosstalk in cardiovascular diseases

2016 ◽  
Vol 310 (7) ◽  
pp. H802-H812 ◽  
Author(s):  
Bryan T. Hackfort ◽  
Paras K. Mishra
Keyword(s):  
Heart Failure ◽  
Hydrogen Sulfide ◽  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
High Dose ◽  
Physiological Level ◽  
Cellular Processes ◽  
Regulatory Rnas ◽  
Apoptosis And Inflammation

Despite an obnoxious smell and toxicity at a high dose, hydrogen sulfide (H2S) is emerging as a cardioprotective gasotransmitter. H2S mitigates pathological cardiac remodeling by regulating several cellular processes including fibrosis, hypertrophy, apoptosis, and inflammation. These encouraging findings in rodents led to initiation of a clinical trial using a H2S donor in heart failure patients. However, the underlying molecular mechanisms by which H2S mitigates cardiac remodeling are not completely understood. Empirical evidence suggest that H2S may regulate signaling pathways either by directly influencing a gene in the cascade or interacting with nitric oxide (another cardioprotective gasotransmitter) or both. Recent studies revealed that H2S may ameliorate cardiac dysfunction by up- or downregulating specific microRNAs. MicroRNAs are noncoding, conserved, regulatory RNAs that modulate gene expression mostly by translational inhibition and are emerging as a therapeutic target for cardiovascular disease (CVD). Few microRNAs also regulate H2S biosynthesis. The inter-regulation of microRNAs and H2S opens a new avenue for exploring the H2S-microRNA crosstalk in CVD. This review embodies regulatory mechanisms that maintain the physiological level of H2S, exogenous H2S donors used for increasing the tissue levels of H2S, H2S-mediated regulation of CVD, H2S-microRNAs crosstalk in relation to the pathophysiology of heart disease, clinical trials on H2S, and future perspectives for H2S as a therapeutic agent for heart failure.

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