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International Journal of Molecular... May 2019Cardiac hypertrophy is an adaptive and compensatory mechanism preserving cardiac output during detrimental stimuli. Nevertheless, long-term stimuli incite chronic... (Review)
Review
Cardiac hypertrophy is an adaptive and compensatory mechanism preserving cardiac output during detrimental stimuli. Nevertheless, long-term stimuli incite chronic hypertrophy and may lead to heart failure. In this review, we analyze the recent literature regarding the role of ERK (extracellular signal-regulated kinase) activity in cardiac hypertrophy. ERK signaling produces beneficial effects during the early phase of chronic pressure overload in response to G protein-coupled receptors (GPCRs) and integrin stimulation. These functions comprise (i) adaptive concentric hypertrophy and (ii) cell death prevention. On the other hand, ERK participates in maladaptive hypertrophy during hypertension and chemotherapy-mediated cardiac side effects. Specific ERK-associated scaffold proteins are implicated in either cardioprotective or detrimental hypertrophic functions. Interestingly, ERK phosphorylated at threonine 188 and activated ERK5 (the big MAPK 1) are associated with pathological forms of hypertrophy. Finally, we examine the connection between ERK activation and hypertrophy in (i) transgenic mice overexpressing constitutively activated RTKs (receptor tyrosine kinases), (ii) animal models with mutated sarcomeric proteins characteristic of inherited hypertrophic cardiomyopathies (HCMs), and (iii) mice reproducing syndromic genetic RASopathies. Overall, the scientific literature suggests that during cardiac hypertrophy, ERK could be a "good" player to be stimulated or a "bad" actor to be mitigated, depending on the pathophysiological context.
Topics: Animals; Cardiomegaly; Humans; MAP Kinase Signaling System; Myocardium
PubMed: 31052420
DOI: 10.3390/ijms20092164 -
Journal of Cellular and Molecular... Mar 2019Cardiac hypertrophy is characterized by an increase in myocyte size in the absence of cell division. This condition is thought to be an adaptive response to cardiac wall... (Review)
Review
Cardiac hypertrophy is characterized by an increase in myocyte size in the absence of cell division. This condition is thought to be an adaptive response to cardiac wall stress resulting from the enhanced cardiac afterload. The pathogenesis of heart dysfunction, which is one of the primary causes of morbidity and mortality in elderly people, is often associated with myocardial remodelling caused by cardiac hypertrophy. In order to well understand the potential mechanisms, we described the molecules involved in the development and progression of myocardial hypertrophy. Increasing evidence has indicated that micro-RNAs are involved in the pathogenesis of cardiac hypertrophy. In addition, molecular biomarkers including vascular endothelial growth factor B, NAD-dependent deacetylase sirtuin-3, growth/differentiation factor 15 and glycoprotein 130, also play important roles in the development of myocardial hypertrophy. Knowing the regulatory mechanisms of these biomarkers in the heart may help identify new molecular targets for the treatment of cardiac hypertrophy.
Topics: Animals; Biomarkers; Cardiomegaly; Humans
PubMed: 30648807
DOI: 10.1111/jcmm.14129 -
Medical Science Monitor Basic Research Jul 2016Ventricular hypertrophy is an ominous escalation of hemodynamically stressful conditions such as hypertension and valve disease. The pathophysiology of hypertrophy is... (Review)
Review
Ventricular hypertrophy is an ominous escalation of hemodynamically stressful conditions such as hypertension and valve disease. The pathophysiology of hypertrophy is complex and multifactorial, as it touches on several cellular and molecular systems. Understanding the molecular background of cardiac hypertrophy is essential in order to protect the myocardium from pathological remodeling, or slow down the destined progression to heart failure and cardiomyopathy. In this review we highlight the most important molecular aspects of cardiac hypertrophic growth in light of the currently available published research data.
Topics: Animals; Cardiomegaly; Humans; Myocardium
PubMed: 27450399
DOI: 10.12659/MSMBR.900437 -
Canadian Journal of Physiology and... Feb 2020The heart is capable of responding to stressful situations by increasing muscle mass, which is broadly defined as cardiac hypertrophy. This phenomenon minimizes... (Review)
Review
The heart is capable of responding to stressful situations by increasing muscle mass, which is broadly defined as cardiac hypertrophy. This phenomenon minimizes ventricular wall stress for the heart undergoing a greater than normal workload. At initial stages, cardiac hypertrophy is associated with normal or enhanced cardiac function and is considered to be adaptive or physiological; however, at later stages, if the stimulus is not removed, it is associated with contractile dysfunction and is termed as pathological cardiac hypertrophy. It is during physiological cardiac hypertrophy where the function of subcellular organelles, including the sarcolemma, sarcoplasmic reticulum, mitochondria, and myofibrils, may be upregulated, while pathological cardiac hypertrophy is associated with downregulation of these subcellular activities. The transition of physiological cardiac hypertrophy to pathological cardiac hypertrophy may be due to the reduction in blood supply to hypertrophied myocardium as a consequence of reduced capillary density. Oxidative stress, inflammatory processes, Ca-handling abnormalities, and apoptosis in cardiomyocytes are suggested to play a critical role in the depression of contractile function during the development of pathological hypertrophy.
Topics: Animals; Apoptosis; Calcium; Cardiomegaly; Cytokines; Humans; Intracellular Space
PubMed: 31815523
DOI: 10.1139/cjpp-2019-0566 -
International Journal of Molecular... Sep 2019Like other organs, the heart undergoes normal adaptive remodeling, such as cardiac hypertrophy, with age. This remodeling, however, is intensified under stress and... (Review)
Review
Like other organs, the heart undergoes normal adaptive remodeling, such as cardiac hypertrophy, with age. This remodeling, however, is intensified under stress and pathological conditions. Cardiac remodeling could be beneficial for a short period of time, to maintain a normal cardiac output in times of need; however, chronic cardiac hypertrophy may lead to heart failure and death. MicroRNAs (miRNAs) are known to have a role in the regulation of cardiac hypertrophy. This paper reviews recent advances in the field of miRNAs and cardiac hypertrophy, highlighting the latest findings for targeted genes and involved signaling pathways. By targeting pro-hypertrophic genes and signaling pathways, some of these miRNAs alleviate cardiac hypertrophy, while others enhance it. Therefore, miRNAs represent very promising potential pharmacotherapeutic targets for the management and treatment of cardiac hypertrophy.
Topics: Animals; Cardiomegaly; Heart Failure; Humans; MicroRNAs; Signal Transduction
PubMed: 31547607
DOI: 10.3390/ijms20194714 -
The Korean Journal of Internal Medicine Nov 2023
Topics: Humans; Pleural Effusion; Cardiomegaly
PubMed: 37482651
DOI: 10.3904/kjim.2023.092 -
Progress in Biophysics and Molecular... Jan 2021Cardiac hypertrophy, defined as an increase in mass of the heart, is a complex process driven by simultaneous changes in hemodynamics, mechanical stimuli, and hormonal... (Review)
Review
Cardiac hypertrophy, defined as an increase in mass of the heart, is a complex process driven by simultaneous changes in hemodynamics, mechanical stimuli, and hormonal inputs. It occurs not only during pre- and post-natal development but also in adults in response to exercise, pregnancy, and a range of cardiovascular diseases. One of the most exciting recent developments in the field of cardiac biomechanics is the advent of computational models that are able to accurately predict patterns of heart growth in many of these settings, particularly in cases where changes in mechanical loading of the heart play an import role. These emerging models may soon be capable of making patient-specific growth predictions that can be used to guide clinical interventions. Here, we review the history and current state of cardiac growth models and highlight three main limitations of current approaches with regard to future clinical application: their inability to predict the regression of heart growth after removal of a mechanical overload, inability to account for evolving hemodynamics, and inability to incorporate known growth effects of drugs and hormones on heart growth. Next, we outline growth mechanics approaches used in other fields of biomechanics and highlight some potential lessons for cardiac growth modeling. Finally, we propose a multiscale modeling approach for future studies that blends tissue-level growth models with cell-level signaling models to incorporate the effects of hormones in the context of pregnancy-induced heart growth.
Topics: Animals; Biomechanical Phenomena; Cardiomegaly; Computer Simulation; Drug-Related Side Effects and Adverse Reactions; Female; Heart; Hemodynamics; Hormones; Humans; Models, Cardiovascular; Pharmaceutical Preparations; Pregnancy; Regression Analysis; Signal Transduction
PubMed: 32702352
DOI: 10.1016/j.pbiomolbio.2020.07.001 -
Cardiovascular Therapeutics Jun 2012Despite an extensive literature defining the mechanisms and significance of pathological myocardial remodeling, there has been no comprehensive review of the inverse... (Review)
Review
Despite an extensive literature defining the mechanisms and significance of pathological myocardial remodeling, there has been no comprehensive review of the inverse process, often labeled reverse remodeling. Accordingly, the goal of this review is to overview the varied settings in which clinically significant reverse remodeling has been well documented. When available, we reviewed relevant randomized, controlled clinical trials, and meta-analyses with sufficient cardiac imaging data to permit conclusions about reverse remodeling. When these types of studies were not available, relevant case-control studies and case series that employed appropriate methodology were reviewed. Regression of pathological myocardial hypertrophy, chamber shape distortions, and dysfunction occurs in a wide variety of settings. Although reverse remodeling occurs spontaneously in some etiologies of myocardial dysfunction and failure, remodeling is more commonly observed in response to medical, device-based, or surgical therapies, including β-blockers, revascularization, cardiac resynchronization therapy, and valve surgery. Indeed, reverse remodeling following pathophysiologically targeted interventions helps validate that the targeted mechanisms are propelling and/or sustaining pathological remodeling. The diverse clinical settings in which reverse remodeling has been observed demonstrates that myocardial remodeling is bidirectional and occurs across the full spectrum of myocardial disease severity, duration, and etiology. Observations in several settings suggest that recovered hearts are not truly normal despite parallel improvements at organ, tissue, and cellular level. Nevertheless, the link between reverse remodeling and improved outcomes should inspire further research to better understand the mechanisms responsible for both reverse remodeling and persistent deviations from normalcy.
Topics: Animals; Cardiomegaly; Heart Diseases; Humans; Myocardium; Recovery of Function; Treatment Outcome; Ventricular Remodeling
PubMed: 21108773
DOI: 10.1111/j.1755-5922.2010.00247.x -
Virchows Archiv : An International... Jul 2021Since cardiac hypertrophy may be considered a cause of death at autopsy, its assessment requires a uniform approach. Common terminology and methodology to measure the...
Since cardiac hypertrophy may be considered a cause of death at autopsy, its assessment requires a uniform approach. Common terminology and methodology to measure the heart weight, size, and thickness as well as a systematic use of cut off values for normality by age, gender, and body weight and height are needed. For these reasons, recommendations have been written on behalf of the Association for European Cardiovascular Pathology. The diagnostic work up implies the search for pressure and volume overload conditions, compensatory hypertrophy, storage and infiltrative disorders, and cardiomyopathies. Although some gross morphologic features can point to a specific diagnosis, systematic histologic analysis, followed by possible immunostaining and transmission electron microscopy, is essential for a final diagnosis. If the autopsy is carried out in a general or forensic pathology service without expertise in cardiovascular pathology, the entire heart (or pictures) together with mapped histologic slides should be sent for a second opinion to a pathologist with such an expertise. Indication for postmortem genetic testing should be integrated into the multidisciplinary management of sudden cardiac death.
Topics: Autopsy; Cardiomegaly; Cause of Death; Genetic Testing; Humans; Myocardium; Organ Size; Predictive Value of Tests; Risk Factors; Terminology as Topic
PubMed: 33740097
DOI: 10.1007/s00428-021-03038-0 -
Cells May 2022Cardiovascular diseases are a major health problem, and long-term survival for people diagnosed with heart failure is, still, unrealistic. Pathological cardiac... (Review)
Review
Cardiovascular diseases are a major health problem, and long-term survival for people diagnosed with heart failure is, still, unrealistic. Pathological cardiac hypertrophy largely contributes to morbidity and mortality, as effective therapeutic approaches are lacking. Non-coding RNAs (ncRNAs) arise as active regulators of the signaling pathways and mechanisms that govern this pathology, and their therapeutic potential has received great attention in the last decades. Preclinical studies in large animal models have been successful in ameliorating cardiac hypertrophy, and an antisense drug for the treatment of heart failure has, already, entered clinical trials. In this review, we provide an overview of the molecular mechanisms underlying cardiac hypertrophy, the involvement of ncRNAs, and the current therapeutic landscape of oligonucleotides targeting these regulators. Strategies to improve the delivery of such therapeutics and overcome the actual challenges are, also, defined and discussed. With the fast advance in the improvement of oligonucleotide drug delivery, the inclusion of ncRNAs-targeting therapies for cardiac hypertrophy seems, increasingly, a closer reality.
Topics: Animals; Cardiomegaly; Cardiovascular Diseases; Heart Failure; Humans; RNA, Untranslated; Signal Transduction
PubMed: 35681500
DOI: 10.3390/cells11111805