Mechanisms for the transition from physiological to pathological cardiac hypertrophy

Abstract

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 2+ -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.Key words: cardiac hypertrophy, cardiac remodeling, pathological cardiac hypertrophy, physiological cardiac hypertrophy, adaptive cardiac hypertrophy, cardiac contractile function.Résumé : Le coeur est capable de réagir à des situations de stress par une augmentation de sa masse musculaire, que l'on caractérise plus largement comme étant de l'hypertrophie cardiaque. Ce phénomène permet de réduire au minimum la tension de la paroi ventriculaire dans un coeur soumis à une charge de travail plus élevée que normalement. Aux premiers stades, l'hypertrophie cardiaque est associée avec une fonction cardiaque normale ou améliorée et est considérée comme étant adaptative ou physiologique; toutefois, à des stades plus tardifs, si le stimulus n'est pas écarté, elle est associée avec un dysfonctionnement contractile et alors nommée hypertrophie cardiaque pathologique. C'est pendant l'hypertrophie cardiaque physiologique que le fonctionnement des organites sous-cellulaires, y compris le sarcolemme, le réticulum sarcoplasmique, les mitochondries et les myofibrilles peut être régulé à la hausse, tandis que l'hypertrophie cardiaque pathologique est associée avec une régulation à la baisse de ces activités sous-cellulaires. La transition de l'hypertrophie cardiaque physiologique vers l'hypertrophie cardiaque pathologique pourrait être le fait d'une diminution de l'apport sanguin au myocarde hypertrophié comme conséquence de la diminution de la densité des capillaires. On laisse entendre que le stress oxydatif, les processus inflammatoires, les anomalies de la gestion des ions Ca 2+ dans les cardiomyocytes ainsi que l'apoptose joueraient des rôles critiques dans la dépression de la fonction contractile au cours du développement de l'hypertrophie pathologique. [Traduit par...

Downregulation of miR-26b-5p, miR-204-5p, and miR-497-3p Expression Facilitates Exercise-Induced Physiological Cardiac Hypertrophy by Augmenting Autophagy in Rats

“…The 10-week moderate-intensity swimming exercise enlarged and thickened cardiomyocytes. Although an increase in cardiomyocyte volume is also observed in pathological cardiomegaly, increased fetal gene expression such as ANP, BNP, b-MHC were also significantly upregulated in pathological LVH (Swynghedauw, 1986;Dorn et al, 1994;Bernardo et al, 2010;Nakamura and Sadoshima, 2018;Oldfield et al, 2019). In our swimming exercise-induced cardiomyocyte hypertrophy, the expression of ANP, a-actin, and the ratio of b-MHC to a-MHC was not significantly changed, indicating a physiological LVH model was successfully induced.…”

“…Both of them have an increased myocyte volume and heart size. The difference is that physiological LVH is induced by aerobic exercise training, postnatal growth, and pregnancy, and characterized by unchanged fetal and apoptosis gene expression and increased cardiac function while pathological LVH is stimulated by pressure or volume overload or cardiomyopathy, and characterized by apoptosis and fibrosis and depressed cardiac function (Bernardo et al, 2010;Nakamura and Sadoshima, 2018;Oldfield et al, 2019). For example, LVH induced by swimming exercise training is an adaption for a chronic increase in hemodynamic overload (Xiao et al, 2014;Bernardo et al, 2018), whereas myocardial infarction induced pathological LVH is associated with increased fibrosis, lowered aerobic capacity, and maladaptive remodeling (McMullen and Izumo, 2006;Dorn, 2007;Schiattarella and Hill, 2015).…”

tRNA-Derived Small RNAs and Their Potential Roles in Cardiac Hypertrophy

“…ANG is a major inducer of tRNA halves (Thompson et al, 2008;Fu et al, 2009;Yamasaki et al, 2009;Su et al, 2019), and several studies suggest ANG is involved in cardiac hypertrophy and heart failure (Patel et al, 2008;Jiang et al, 2014;Yu et al, 2018;Oldfield et al, 2020). ANG not only functions as an RNase, but is also a potent stimulus for angiogenesis (Tello-Montoliu et al, 2006).…”

“…ANG not only functions as an RNase, but is also a potent stimulus for angiogenesis (Tello-Montoliu et al, 2006). Pro-angiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and ANG, are involved in the development of cardiac hypertrophy (Oldfield et al, 2020). Cardiomyocytes secret pro-angiogenic molecules to support vascular growth to increase blood flow in the hypertrophic heart (Oldfield et al, 2020).…”

Single-cell RNA-sequencing Unravels Heterogeneity of Cardiomyocytes and Signaling Pathways in Pressure Overload

“…Despite continuous improvements in the diagnosis and treatment of cardiac hypertrophy, the mortality is close to 25% to 50% within 5 years following diagnosis [8]. Elucidation concerning the complex signaling mechanisms during myocardial hypertrophy may accelerate the improvement in treatment, thereby improving the quality of life of patients with cardiac hypertrophy [9]. Thus, it is urgent and necessary to probe out novel and effective therapeutic targets for preventing and cutting down pathological cardiac hypertrophy.…”