Genetic Factors in Cardiac Hypertrophy

Abstract

Cardiac hypertrophy is an adaptive response to any cardiac insult or stress that increases hemodynamic load. Cardiac hypertrophy can exist in a state of compensation or progress to a decompensated state (i.e., heart failure) over time. It has been established through transgenic overexpression and gene ablation studies that multiple signaling pathways are involved in the induction of hypertrophy as well as its decompensation. This article reviews the role of G alpha q in the development of pressure overload hypertrophy and discusses the relationships between G alpha q and beta-adrenergic receptors, RGS proteins, and the proapoptotic factor, Nix/Bnip3L.

Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy

“…C ardiac hypertrophy is a common adaptive response of the heart to injury and hemodynamic stress (1,2). Hypertrophic remodeling can be concentric (characterized addition of sarcomeres in parallel and lateral growth of individual myocytes) or eccentric (characterized by addition of sarcomeres in series and longitudinal cell growth) (3).…”

“…Hypertrophic remodeling can be concentric (characterized addition of sarcomeres in parallel and lateral growth of individual myocytes) or eccentric (characterized by addition of sarcomeres in series and longitudinal cell growth) (3). At the cellular level, hypertrophy is characterized by increased cell size/protein content and reactivation of fetal genes (e.g., ANF, BNP) (2,4). Although initially compensatory, hypertrophy can eventually lead to decompensation characterized by heart failure, arrhythmias, and death (1,2,5).…”

“…At the cellular level, hypertrophy is characterized by increased cell size/protein content and reactivation of fetal genes (e.g., ANF, BNP) (2,4). Although initially compensatory, hypertrophy can eventually lead to decompensation characterized by heart failure, arrhythmias, and death (1,2,5). Although a number of therapies are now available, cardiac hypertrophy and its attendant consequences remain a source of considerable morbidity and mortality (3,6).…”

“…These studies have established that the hypertrophic response occurs through the activation of multiple cytosolic signaling pathways and nuclear factors (1,2,7). With respect to the latter, factors such as myocyte enhancer factor-2 (MEF2), GATA4, and nuclear factor of activated T cells (NFATs) have been implicated as key mediators of the hypertrophic transcriptional program (8)(9)(10)(11)(12)(13)(14)(15).…”

“…It is known that hypertrophic stimulation can reduce expression of certain postnatal genes with reinduction of fetal genes (2,4,28,30,31). To determine the effect of cardiac hypertrophy on KLF15 expression in the heart, transaortic constriction (TAC) studies were performed in adult rats.…”