Molecular Mechanisms of Subcellular Remodeling in Congestive Heart Failure

Abstract

Cardiac dysfunction in congestive heart failure (CHF) is generally associated with changes in the biochemical activity of different subcellular organelles including the sarcolemma (SL), sarcoplasmic reticulum (SR), and myofibrils (MF). Extensive research has been carried out by employing a wide variety of experimental models as well as myocardial tissue from patients with CHF to examine if changes in the activities of subcellular organelles are due to corresponding changes in cardiac protein content and gene expression. Varying degrees of alterations in mRNA levels and protein content for SL, SR, and MF have been observed in the failing heart. Furthermore, improvement in cardiac function in CHF by different pharmacologic interventions has been associated with attenuation of changes in gene and protein expression for SL, SR, and MF. These observations are consistent with the view that subcellular remodeling and subsequent ­cardiac dysfunction in CHF may be a consequence of alterations in cardiac gene expression.