Growth Regulation of Cardiomyocytes: Control of Cell Size and Its Role in Cardiac Hypertrophy

Abstract

Cardiac hypertrophy in its pure sense describes the ability of cardiomyocytes to increase their cell shape in the absence of cell proliferation. As the large majority of mammalian cardiomyocytes lose the ability to cytokinesis shortly after birth, this is the most important process by which the heart muscle mass can be adapted to increased mechanical stress. Cardiac hypertrophy is a physiological process during adolescence in which the total heart size is increased nearly eightfold from birth to adolescence, but there is only a limited ability of the adult heart to further increase heart size without getting dysfunctional. As cardiac hypertrophy is an established risk factor for heart failure, a lot of attention has been dropped to identify key pathways that trigger cardiac hypertrophy and the transition from physiological hypertrophy to pathophysiological hypertrophy. A large number of hormones, cytokines and neurotransmitters have been identified that trigger cardiac hypertrophy and specifically those related to the sympathetic nervous system, and the renin-angiotensin system is of importance for the transition to heart failure. An increase in the translational capacity is the basis of cardiac growth, but changes in the expression, mainly linked to the sarcomere but also linked to cardiac metabolism, characterise pathophysiological hypertrophy. Although initially not considered as a realistic perspective, it is clear meanwhile that even pathophysiological hypertrophy is a reversible process. The main challenge for the future is to indentify key pathways that normalise heart sizes and normalise the cardiac phenotypes. This chapter reviews our current understanding of key processes leading to cardiac hypertrophy.