Recent Advances in Cardiac Myocyte Biology and Function

Abstract

Cardiac myocyte dysfunction is the underlying cause of changes in cardiac contractility associated with several pathological conditions. Hence, the physiology of cardiac myocytes has been the subject of intense investigation and much attention has been paid to important questions such as the following: what maintains and regulates the structural and functional integrity of cardiac myocytes?; how do myocytes respond to stress?; what are the molecular changes that contribute to myocytes dysfunction in cardiac disease?; how can pathological changes in myocytes be prevented or attenuated?; what determines myocyte life and death?; and can adult myocytes be renewed or replenished? Recent advancements in the field continue to address these important issues.1–18 Cardiac myocyte hypertrophy has been an area of intense interest for a long time,19 because it is well-known that maladaptive cardiac myocyte hypertrophy and accompanying cardiac remodeling often lead to heart failure.20,21 Recent studies have uncovered new mechanisms of myocyte hypertrophy. For instance, Matsushima et al22 showed that increased nuclear oxidative stress caused by nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) leads to oxidation and nuclear export of histone deacetylase 4 (a class II histone deacetylase), which is a repressor of transcription factors involved in hypertrophic response (eg, nuclear factor of activated T-cells); this suggest that inhibition of Nox4 can be another avenue for dampening maladaptive cardiac hypertrophy. G-protein–coupled receptor kinase-5 (GRK5) is another important regulator/kinase of a class II histone deacetylase 5 and its contribution to cardiac hypertrophy had been implicated previously.23 Recently, Gold et al24 have used both global and cardiac-specific Grk5 knockout mice to test the requirement of this protein for pathological hypertrophy. In response to pressure overload, Grk5 knockout mice showed attenuated hypertrophy, remodeling, and hypertrophy-related gene expression, clearly demonstrating the essential role of this protein in …