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Nature Reviews. Cardiology Jul 2018Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number,... (Review)
Review
Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure. Each form of hypertrophy is regulated by distinct cellular signalling pathways. In the past decade, a growing number of studies have suggested that previously unrecognized mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune responses, translational regulation, and epigenetic modifications, positively or negatively regulate cardiac hypertrophy. In this Review, we summarize the underlying molecular mechanisms of physiological and pathological hypertrophy, with a particular emphasis on the role of metabolic remodelling in both forms of cardiac hypertrophy, and we discuss how the current knowledge on cardiac hypertrophy can be applied to develop novel therapeutic strategies to prevent or reverse pathological hypertrophy.
Topics: Adaptation, Physiological; Animals; Cardiomegaly; Cardiomegaly, Exercise-Induced; Energy Metabolism; Heart Ventricles; Humans; Mitochondria, Heart; Myocardium; Regeneration; Signal Transduction; Ventricular Remodeling
PubMed: 29674714
DOI: 10.1038/s41569-018-0007-y -
High Blood Pressure & Cardiovascular... Mar 2015Obesity can be regarded as an energy balance disorder in which inappropriate expansion and dys-function of adipose tissue lead to unfavorable outcomes. Even in the... (Review)
Review
Obesity can be regarded as an energy balance disorder in which inappropriate expansion and dys-function of adipose tissue lead to unfavorable outcomes. Even in the absence of hypertension, adiposity induces structural and functional changes in the heart through hemodynamic and non hemodynamic factors. In the "obese" heart, besides the growth of cardiomyocytes, interstitial fat infiltration and triglyceride accumulation in the contractile elements importantly contribute to left-ventricular mass (LVM) accrual, hypertrophy (LVH) and geometric pattern. In harmony with this, the likelihood of LVH is greater in either obese normotensive or hypertensive individuals than in their non-obese counterparts. Interestingly, recent observations highlight the increasing prevalence of the "concentric" (ie, combined remodeling and hypertrophy), rather than "eccentric" pattern of LV geometry in obesity. Nonetheless, obesity is linked with lack of decrease, or even increase, of LVM over time, independently of blood pressure control and hypertensive treatment. Although obesity-related LV changes result in progressive systolic and diastolic heart failure, the assessment of LVM and LVH in obese individuals still remains a difficult task. In this scenario, it is tempting to speculate that therapeutic interventions for reversal of LVH in obesity should either overcome the "non-hemodynamic" factors or reduce the hemodynamic load. Indeed, weight loss, either achieved by lifestyle changes or bariatric procedures, decreases LVM and improves LV function regardless of blood pressure status. These and other mechanistic insights are discussed in this review, which focuses on "adipose dysfunction" as potential instigator of, and putative therapeutic target for, LVH regression in the setting of obesity.
Topics: Adipose Tissue; Adiposity; Animals; Energy Metabolism; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Obesity; Prognosis; Risk Factors; Ventricular Function, Left; Ventricular Remodeling
PubMed: 25117210
DOI: 10.1007/s40292-014-0068-x -
The International Journal of... Apr 2018There are a number of diseases which can increase left ventricular myocardial wall thickness through a number of different mechanisms. Multi-parametric mapping... (Review)
Review
There are a number of diseases which can increase left ventricular myocardial wall thickness through a number of different mechanisms. Multi-parametric mapping techniques are a new addition to the cardiovascular magnetic resonance (CMR) armoury with a number of potential clinical roles. In this review article, we will explore the role of imaging in left ventricular hypertrophy, and particularly developments in CMR. We focus on ability of CMR to characterize myocardial tissue using multiparametric mapping (native T1, T2 and extracellular volume mapping), to bridge from the microscopic histological domain and into the clinical domain of non-invasive imaging.
Topics: Cardiomyopathies; Contrast Media; Fibrosis; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Predictive Value of Tests; Prognosis; Ventricular Function, Left; Ventricular Remodeling
PubMed: 29500729
DOI: 10.1007/s10554-018-1320-6 -
Current Hypertension Reports Jun 2009The renin-angiotensin system (RAS), an important control system for blood pressure and intravascular volume, also causes left ventricular hypertrophy (LVH) and fibrosis.... (Review)
Review
The renin-angiotensin system (RAS), an important control system for blood pressure and intravascular volume, also causes left ventricular hypertrophy (LVH) and fibrosis. The main causal mechanism is the increase in blood pressure, which leads to increased left ventricular wall stress; however, aldosterone release from the adrenals and (more controversially) the direct action of angiotensin II on the cardiomyocytes also play a role. Large clinical trials evaluating the blockade of the RAS with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated an ability to prevent progression and induce regression of left ventricular mass, thereby reducing the significant and independent cardiovascular risk conferred by LVH. Regression of left ventricular mass is also achieved by other medication classes, but the RAS blockers have an additional beneficial effect for the same blood pressure reduction, for which the mechanism is not entirely clear. Studies comparing the efficacy of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers to achieve LVH regression have not demonstrated any clear benefit of one class over the other.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Renin-Angiotensin System; Treatment Outcome
PubMed: 19442324
DOI: 10.1007/s11906-009-0030-9 -
Giornale Italiano Di Cardiologia Mar 1988
Topics: Adaptation, Physiological; Cardiomegaly; Heart Ventricles; Humans; Sports Medicine
PubMed: 2971589
DOI: No ID Found -
Circulation Journal : Official Journal... 2013
Topics: Hair; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Magnesium; Male; Renal Dialysis
PubMed: 24200847
DOI: 10.1253/circj.cj-13-1294 -
Future Cardiology Sep 2009Distinguishing physiological left ventricular hypertrophy of an athlete's heart from that of pathological left ventricular (hypertrophic cardiomyopathy) can be difficult... (Review)
Review
Distinguishing physiological left ventricular hypertrophy of an athlete's heart from that of pathological left ventricular (hypertrophic cardiomyopathy) can be difficult despite the advent of new imaging techniques. Nevertheless, the final diagnosis is of utmost importance as it will have a profound impact on an individual's life. A diagnosis of hypertrophic cardiomyopathy essentially excludes an individual from sport and strenuous exertion and necessitates the need for further tests and treatment, as well as the screening of family members. Hypertrophic cardiomyopathy remains the most common cause of a pathologically hypertrophied heart in young athletes, with a prevalence of one in 500. The issue of sudden death in athletes due to pathological left ventricular hypertrophy and hypertrophic cardiomyopathy has recently gained recognition owing to the death of several word class athletes during sporting participation. What compounds this further is the fact that a proportion of athletes fall into the 'grey zone' (ventricular wall thickness of 13-16 mm) where the increase in cardiac size overlaps with the phenotypic variation of hypertrophic cardiomyopathy - making echocardiographic differentiation of the two entities challenging. This review discusses the echocardiographic differentiation of the athlete's heart, including physiological left ventricular hypertrophy from pathological left ventricular hypertrophy. Although several of the cardiomyopathies cause pathological left ventricular hypertrophy, focus will be given to hypertrophic cardiomyopathy, for reasons mentioned above. Discussion will also focus on the newer and emerging echocardiographic techniques for this purpose. The term 'hypertrophic cardiomyopathy' is used to describe the nonobstuctive form of hypertrophic cardiomyopathy as this review article focuses on distinguishing the 'mild' form of hypertrophic cardiomyopathy from an athlete's heart. When the more severe obstructive form is being described, the term 'hypertrophic obstructive cardiomyopathy' is used.
Topics: Cardiomyopathy, Hypertrophic; Diagnosis, Differential; Echocardiography; Echocardiography, Doppler; Echocardiography, Three-Dimensional; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Sex Factors
PubMed: 19715413
DOI: 10.2217/fca.09.34 -
Circulation Mar 2008
Review
Topics: Aging; Animals; Biomarkers; Cardiovascular Diseases; Diagnostic Imaging; Dogs; Fetal Heart; Heart Function Tests; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Myocardial Contraction; Natriuretic Peptide, Brain; Pulmonary Artery; Tricuspid Valve; Ventricular Dysfunction, Right; Ventricular Function; Ventricular Function, Right
PubMed: 18347220
DOI: 10.1161/CIRCULATIONAHA.107.653576 -
Cardiovascular Research Feb 2020In patients with pulmonary hypertension, right ventricular hypertrophy (RVH) is a detrimental condition that ultimately results in right heart failure and death. The...
AIMS
In patients with pulmonary hypertension, right ventricular hypertrophy (RVH) is a detrimental condition that ultimately results in right heart failure and death. The ubiquitin proteasome system has been identified as a major protein degradation system to regulate cardiac remodelling in the left heart. Its role in right heart hypertrophy, however, is still ambiguous.
METHODS AND RESULTS
RVH was induced in mice by pulmonary artery banding (PAB). Both, expression and activity of the proteasome was found to be up-regulated in the hypertrophied right ventricle (RV) compared to healthy controls. Catalytic inhibition of the proteasome by the two proteasome inhibitors Bortezomib (BTZ) and ONX-0912 partially improved RVH both in preventive and therapeutic applications. Native gel analysis revealed that specifically the 26S proteasome complexes were activated in experimental RVH. Increased assembly of 26S proteasomes was accompanied by elevated expression of Rpn6, a rate-limiting subunit of 26S proteasome assembly, in hypertrophied cardiomyocytes of the right heart. Intriguingly, patients with RVH also showed increased expression of Rpn6 in hypertrophied cardiomyocytes of the RV as identified by immunohistochemical staining.
CONCLUSION
Our data demonstrate that alterations in expression and activity of proteasomal subunits play a critical role in the development of RVH. Moreover, this study provides an improved understanding on the selective activation of the 26S proteasome in RVH that might be driven by the rate-limiting subunit Rpn6. In RVH, Rpn6 therefore represents a more specific target to interfere with proteasome function than the commonly used catalytic proteasome inhibitors.
Topics: Animals; Disease Models, Animal; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Inflammation Mediators; Mice; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Signal Transduction; Ubiquitination; Ventricular Function, Right; Ventricular Remodeling
PubMed: 31020333
DOI: 10.1093/cvr/cvz103 -
European Heart Journal Apr 1982
Review
Topics: Cardiomegaly; Echocardiography; Heart Ventricles; Humans; Myocardial Contraction; Prospective Studies; Radiography
PubMed: 6210549
DOI: 10.1093/eurheartj/3.suppl_a.49