scholarly journals Noncoding RNAs regulating cardiac muscle mass

2019 ◽  
Vol 127 (2) ◽  
pp. 633-644 ◽  
Author(s):  
Glenn D. Wadley ◽  
Séverine Lamon ◽  
Sarah E. Alexander ◽  
Julie R. McMullen ◽  
Bianca C. Bernardo
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiac Hypertrophy ◽  
Cardiac Muscle ◽  
Muscle Mass ◽  
Targeted Delivery ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
The Body ◽  
Circular Rnas

Noncoding RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) play roles in the development and homeostasis of nearly every tissue of the body, including the regulation of processes underlying heart growth. Cardiac hypertrophy can be classified as either physiological (beneficial heart growth) or pathological (detrimental heart growth), the latter of which results in impaired cardiac function and heart failure and is predictive of a higher incidence of death due to cardiovascular disease. Several miRNAs have a functional role in exercise-induced cardiac hypertrophy, while both miRNAs and lncRNAs are heavily involved in pathological heart growth and heart failure. The latter have the potential to act as an endogenous sponge RNA and interact with specific miRNAs to control cardiac hypertrophy, adding another level of complexity to our understanding of the regulation of cardiac muscle mass. In addition to tissue-specific effects, ncRNA-mediated tissue cross talk occurs via exosomes. In particular, miRNAs can be internalized in exosomes and secreted from various cardiac and vascular cell types to promote angiogenesis, as well as protection and repair of ischemic tissues. ncRNAs hold promising therapeutic potential to protect the heart against ischemic injury and aid in regeneration. Numerous preclinical studies have demonstrated the therapeutic potential of ncRNAs, specifically miRNAs, for the treatment of cardiovascular disease. Most of these studies employ antisense oligonucleotides to inhibit miRNAs of interest; however, off-target effects often limit their potential to be translated to the clinic. In this context, approaches using viral and nonviral delivery tools are promising means to provide targeted delivery in vivo.

scholarly journals Regulatory RNAs in Heart Failure

Circulation ◽  
2020 ◽  
Vol 141 (4) ◽  
pp. 313-328 ◽  
Author(s):  
Clarissa Pedrosa da Costa Gomes ◽  
Blanche Schroen ◽  
Gabriela M. Kuster ◽  
Emma L. Robinson ◽  
Kerrie Ford ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Noncoding Rna ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Regulatory Rna ◽  
Messenger Rnas ◽  
Protein Coding

Cardiovascular disease is an enormous socioeconomic burden worldwide and remains a leading cause of mortality and disability despite significant efforts to improve treatments and personalize healthcare. Heart failure is the main manifestation of cardiovascular disease and has reached epidemic proportions. Heart failure follows a loss of cardiac homeostasis, which relies on a tight regulation of gene expression. This regulation is under the control of multiple types of RNA molecules, some encoding proteins (the so-called messenger RNAs) and others lacking protein-coding potential, named noncoding RNAs. In this review article, we aim to revisit the notion of regulatory RNA, which has been thus far mainly confined to noncoding RNA. Regulatory RNA, which we propose to abbreviate as regRNA, can include both protein-coding RNAs and noncoding RNAs, as long as they contribute, directly or indirectly, to the regulation of gene expression. We will address the regulation and functional role of messenger RNAs, microRNAs, long noncoding RNAs, and circular RNAs (ie, regRNAs) in heart failure. We will debate the utility of regRNAs to diagnose, prognosticate, and treat heart failure, and we will provide directions for future work.

scholarly journals Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1713 ◽  
Author(s):  
Timothy A. McKinsey ◽  
Thomas M. Vondriska ◽  
Yibin Wang
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Loss Of Function ◽  
Sequencing Technologies ◽  
Recent Developments ◽  
Non Coding Rnas ◽  
Epigenomic Regulation ◽  
Generation Sequencing ◽  
Epigenetic Processes

Epigenetic processes are known to have powerful roles in organ development across biology. It has recently been found that some of the chromatin modulatory machinery essential for proper development plays a previously unappreciated role in the pathogenesis of cardiac disease in adults. Investigations using genetic and pharmacologic gain- and loss-of-function approaches have interrogated the function of distinct epigenetic regulators, while the increased deployment of the suite of next-generation sequencing technologies have fundamentally altered our understanding of the genomic targets of these chromatin modifiers. Here, we review recent developments in basic and translational research that have provided tantalizing clues that may be used to unlock the therapeutic potential of the epigenome in heart failure. Additionally, we provide a hypothesis to explain how signal-induced crosstalk between histone tail modifications and long non-coding RNAs triggers chromatin architectural remodeling and culminates in cardiac hypertrophy and fibrosis.

scholarly journals Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure

2017 ◽  
Vol 114 (45) ◽  
pp. 12033-12038 ◽  
Author(s):  
Iacopo Gesmundo ◽  
Michele Miragoli ◽  
Pierluigi Carullo ◽  
Letizia Trovato ◽  
Veronica Larcher ◽  
...  
Keyword(s):  
Heart Failure ◽  
Growth Hormone ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Therapeutic Potential ◽  
Growth Hormone Releasing Hormone ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction

It has been shown that growth hormone-releasing hormone (GHRH) reduces cardiomyocyte (CM) apoptosis, prevents ischemia/reperfusion injury, and improves cardiac function in ischemic rat hearts. However, it is still not known whether GHRH would be beneficial for life-threatening pathological conditions, like cardiac hypertrophy and heart failure (HF). Thus, we tested the myocardial therapeutic potential of GHRH stimulation in vitro and in vivo, using GHRH or its agonistic analog MR-409. We show that in vitro, GHRH(1-44)NH2 attenuates phenylephrine-induced hypertrophy in H9c2 cardiac cells, adult rat ventricular myocytes, and human induced pluripotent stem cell-derived CMs, decreasing expression of hypertrophic genes and regulating hypertrophic pathways. Underlying mechanisms included blockade of Gq signaling and its downstream components phospholipase Cβ, protein kinase Cε, calcineurin, and phospholamban. The receptor-dependent effects of GHRH also involved activation of Gαs and cAMP/PKA, and inhibition of increase in exchange protein directly activated by cAMP1 (Epac1). In vivo, MR-409 mitigated cardiac hypertrophy in mice subjected to transverse aortic constriction and improved cardiac function. Moreover, CMs isolated from transverse aortic constriction mice treated with MR-409 showed improved contractility and reversal of sarcolemmal structure. Overall, these results identify GHRH as an antihypertrophic regulator, underlying its therapeutic potential for HF, and suggest possible beneficial use of its analogs for treatment of pathological cardiac hypertrophy.

Abstract 16205: MKP-5 Deficiency Attenuates Pressure Overload-induced Cardiac Hypertrophy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kisuk Min ◽  
Yan Huang ◽  
Frank J Giordano ◽  
Sudip Bajpeyi ◽  
Anton M Bennett
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Cardiac Muscle ◽  
Molecular Mechanisms ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Body Weight Ratio ◽  
Pathological Cardiac Hypertrophy

Introduction: Cardiac remodeling occurs in response to pathological stimuli including chronic pressure overload, subsequently leading to heart failure. Despite considerable research efforts, the molecular mechanisms responsible for heart failure have yet to be fully elucidated. One of the prominent signaling pathways involved in the development of pathological cardiac hypertrophy is the mitogen-activated protein kinases (MAPKs) pathways. The MAPKs are inactivated by the MAPK phosphatases (MKPs) through direct dephosphorylation. Growing evidence suggests the importance of MKP-5 signaling mechanisms in physiological and pathological processes. However, the role of MKP-5 has not been explored in cardiac muscle. The objective of this study is to investigate how MKP-5-mediated MAPK activity contributes to mechanisms responsible for pressure overload-induced cardiac hypertrophy. Hypothesis: We tested the hypothesis that MKP-5 serves as a central regulator of MAPKs in pressure overload-induced cardiac hypertrophy. Methods: To investigate the role of MKP-5 in cardiac muscle, we caused pressure overload-induced cardiac hypertrophy in wild type (mkp-5 +/+ ) mice and MKP-5 deficient mice (mkp-5 -/- ) through transverse aortic constriction (TAC). Cardiac function was evaluated by echocardiographic analysis at 4 weeks after TAC. Cardiac hypertrophy was measured by heart-to-body weight ratio. Interstitial myocardial fibrosis was evaluated by Sirius red stains and expression of fibrogenic genes was determined by quantitative PCR. Results: Echocardiographic analysis showed that the ejection fraction and fractional shortening of mkp-5 +/+ mice significantly decreased by at 4 weeks after TAC. Heart-to-body weight ratio increased in mkp-5 +/+ mice. However, MKP-5-deficient heart was protected from cardiac dysfunction and cardiac hypertrophy induced by TAC. Importantly, the fibrogenic genes were markedly reduced in mkp-5 -/- mice as compared with mkp-5 +/+ mice at 4 weeks after TAC. Conclusions: Collectively, our study demonstrates that MKP-5 deficiency prevents the heart from pressure overload-induced cardiac hypertrophy and suggests that MKP-5 may serve as a novel therapeutic target for treatment of heart disease.

scholarly journals Advances in miR-132-Based Biomarker and Therapeutic Potential in the Cardiovascular System

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaizu Xu ◽  
Chungui Chen ◽  
Ying Wu ◽  
Meifang Wu ◽  
Liming Lin
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular System ◽  
Therapeutic Potential ◽  
Calcium Handling ◽  
Atherosclerotic Cardiovascular Disease ◽  
Clinical Phase ◽  
Phase 1B ◽  
Neuroendocrine Activation ◽  
And Oxidative Stress

Atherosclerotic cardiovascular disease and subsequent heart failure threaten global health and impose a huge economic burden on society. MicroRNA-132 (miR-132), a regulatory RNA ubiquitously expressed in the cardiovascular system, is up-or down-regulated in the plasma under various cardiac conditions and may serve as a potential diagnostic or prognostic biomarker. More importantly, miR-132 in the myocardium has been demonstrated to be a master regulator in many pathological processes of ischemic or nonischemic heart failure in the past decade, such as myocardial hypertrophy, fibrosis, apoptosis, angiogenesis, calcium handling, neuroendocrine activation, and oxidative stress, through downregulating target mRNA expression. Preclinical and clinical phase 1b studies have suggested antisense oligonucleotide targeting miR-132 may be a potential therapeutic approach for ischemic or nonischemic heart failure in the future. This review aims to summarize recent advances in the physiological and pathological functions of miR-132 and its possible diagnostic and therapeutic potential in cardiovascular disease.

scholarly journals Gut Microbiota: A Novel Regulator of Cardiovascular Disease and Key Factor in the Therapeutic Effects of Flavonoids

2021 ◽  
Vol 12 ◽  
Author(s):  
Qinyu Li ◽  
Bing Gao ◽  
Bateer Siqin ◽  
Qian He ◽  
Ru Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Gut Microbiota ◽  
The Body ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Key Factor ◽  
The Relationship ◽  
Infarction Heart

Cardiovascular disease is the main cause of death worldwide, and traditional cardiovascular risk factors cannot fully explain the occurrence of the disease. In recent years, the relationship between gut microbiota and its metabolites and cardiovascular disease has been a hot study topic. The changes in gut microbiota and its metabolites are related to the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. The mechanisms by which gut microbiota and its metabolites influence cardiovascular disease have been reported, although not comprehensively. Additionally, following ingestion, flavonoids are decomposed into phenolic acids that are more easily absorbed by the body after being processed by enzymes produced by intestinal microorganisms, which increases flavonoid bioavailability and activity, consequently affecting the onset of cardiovascular disease. However, flavonoids can also inhibit the growth of harmful microorganisms, promote the proliferation of beneficial microorganisms, and maintain the balance of gut microbiota. Hence, it is important to study the relationship between gut microbiota and flavonoids to elucidate the protective effects of flavonoids in cardiovascular diseases. This article will review the role and mechanism of gut microbiota and its metabolites in the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. It also discusses the potential value of flavonoids in the prevention and treatment of cardiovascular disease following their transformation through gut microbiota metabolism.

CLINICAL AND THERAPEUTIC VALUE OF ADIPOKINES IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2020 ◽  
pp. 5-9
Author(s):  
Ya. M Fylenko
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Adipose Tissue ◽  
Kidney Disease ◽  
Therapeutic Potential ◽  
Interdisciplinary Approach ◽  
Blood Lipid ◽  
The Body ◽  
Incidence And Mortality

This review is devoted to the analysis of the role of adipokines in formation of pathological changes in renal function and structure. The patients with chronic kidney disease have a high risk of cardiovascular disease. Currently, the role of systemic hormonal and metabolic factors in the pathogenesis of the kidneys is growing. A promising area of pathogenetic prevention and treatment of kidney disease is an interdisciplinary approach, whereat the adipokine imbalance is of particular interest. Adipose tissue and its messengers, adipokines, are known to be highly associated with kidney disease. Adipocytes are metabolically active cells, producing the signaling lipids, metabolites and protein factors, i.e. adipokines. The interaction of adipose tissue with the kidney is called the adipose kidney axis, being important for the normal functioning of the body, as well as its response to an injury. It has a strong therapeutic potential in respect of the growing rates of chronic kidney disease. Adipocyte hypertrophy is often accompanied by the development of tissue fibrosis, hypoxia, and secretion of pro−inflammatory cytokines (such as tumor necrosis factor or interleukin, which triggers the cell inflammation). Dysfunction of adipose tissue contributes to the development of cardiovascular disease at the local and systemic levels. Thus, for the early diagnosis of chronic kidney disease into the diagnostic program, in addition to the generally accepted indices, the determination of adipokines: for example, serum leptin, adiponectin, omentin, visfatin, microalbuminuria, blood lipid spectrum, intrarenal and functional status of the kidneys with the assessment of functional renal reserve is recommended to be included. Early detection of the disease, new approaches to its diagnosis and treatment can help in reducing the risk of a high incidence and mortality from renal disease. Key words: chronic kidney disease, nephropathy, adipokines, leptin, resistin, adiponectin, visfatin, omentin.

Intramuscular β2-agonist administration enhances early regeneration and functional repair in rat skeletal muscle after myotoxic injury

2008 ◽  
Vol 105 (1) ◽  
pp. 165-172 ◽  
Author(s):  
James G. Ryall ◽  
Jonathan D. Schertzer ◽  
Tammy M. Alabakis ◽  
Stefan M. Gehrig ◽  
David R. Plant ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Side Effects ◽  
Cardiac Hypertrophy ◽  
Muscle Mass ◽  
Intramuscular Injection ◽  
Therapeutic Potential ◽  
Cardiovascular Effects ◽  
Skeletal Muscle Regeneration ◽  
Cardiovascular Side Effects ◽  
The Right

Systemic administration of β2-adrenoceptor agonists (β2-agonists) can improve skeletal muscle regeneration after injury. However, therapeutic application of β2-agonists for muscle injury has been limited by detrimental cardiovascular side effects. Intramuscular administration may obviate some of these side effects. To test this hypothesis, the right extensor digitorum longus (EDL) muscle from rats was injected with bupivacaine hydrochloride to cause complete muscle fiber degeneration. Five days after injury, half of the injured muscles received an intramuscular injection of formoterol (100 μg). Muscle function was assessed at 7, 10, and 14 days after injury. A single intramuscular injection of formoterol increased muscle mass and force-producing capacity at day 7 by 17 and 91%, respectively, but this effect was transient because these values were not different from control levels at day 10. A second intramuscular injection of formoterol at day 7 prolonged the increase in muscle mass and force-producing capacity. Importantly, single or multiple intramuscular injections of formoterol did not elicit cardiac hypertrophy. To characterize any potential cardiovascular effects of intramuscular formoterol administration, we instrumented a separate group of rats with indwelling radio telemeters. Following an intramuscular injection of formoterol, heart rate increased by 18%, whereas systolic and diastolic blood pressure decreased by 31 and 44%, respectively. These results indicate that intramuscular injection can enhance functional muscle recovery after injury without causing cardiac hypertrophy. Therefore, if the transient cardiovascular effects associated with intramuscular formoterol administration can be minimized, this form of treatment may have significant therapeutic potential for muscle-wasting conditions.

Relaxin and the Cardiovascular System: from Basic Science to Clinical Practice

2020 ◽  
Vol 20 (3) ◽  
pp. 167-184 ◽  
Author(s):  
Rafael Clara Martins ◽  
Mariana Pintalhão ◽  
Adelino Leite-Moreira ◽  
Paulo Castro-Chaves
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular System ◽  
Acute Heart Failure ◽  
Therapeutic Potential ◽  
Peptide Hormone ◽  
Beneficial Effects ◽  
Phase Ii Studies ◽  
Medical Need ◽  
Relaxin 2

The peptide hormone relaxin was originally linked to reproductive physiology, where it is believed to mediate systemic and renal hemodynamic adjustments to pregnancy. Recently, its broad range of effects in the cardiovascular system has been the focus of intensive research regarding its implications under pathological conditions and potential therapeutic potential. An understanding of the multitude of cardioprotective actions prompted the study of serelaxin, recombinant human relaxin-2, for the treatment of acute heart failure. Despite early promising results from phase II studies, recently revealed RELAX-AHF-2 outcomes were rather disappointing and the treatment for acute heart failure remains an unmet medical need. This article reviews the physiologic actions of relaxin on the cardiovascular system and its relevance in the pathophysiology of cardiovascular disease. We summarize the most updated clinical data and discuss future directions of serelaxin for the treatment of acute heart failure. This should encourage additional work to determine how can relaxin's beneficial effects be exploited for the treatment of cardiovascular disease.

scholarly journals Therapeutic Potential of Senolytics in Cardiovascular Disease

2020 ◽  
Author(s):  
Emily Dookun ◽  
João F. Passos ◽  
Helen M. Arthur ◽  
Gavin D. Richardson
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Cardiovascular Health ◽  
Therapeutic Potential ◽  
Senescent Cell ◽  
Apoptosis Induction ◽  
Secretory Phenotype ◽  
Artery Disease

Abstract Ageing is the biggest risk factor for impaired cardiovascular health, with cardiovascular disease being the leading cause of death in 40% of individuals over 65 years old. Ageing is associated with both an increased prevalence of cardiovascular disease including heart failure, coronary artery disease, and myocardial infarction. Furthermore, ageing is associated with a poorer prognosis to these diseases. Genetic models allowing the elimination of senescent cells revealed that an accumulation of senescence contributes to the pathophysiology of cardiovascular ageing and promotes the progression of cardiovascular disease through the expression of a proinflammatory and profibrotic senescence-associated secretory phenotype. These studies have resulted in an effort to identify pharmacological therapeutics that enable the specific elimination of senescent cells through apoptosis induction. These senescent cell apoptosis-inducing compounds are termed senolytics and their potential to ameliorate age-associated cardiovascular disease is the focus of this review.

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