Role of Subcellular Remodeling in Cardiac Dysfunction due to Congestive Heart Failure

Abstract

Although alterations in the size and shape of the heart (cardiac remodeling) are considered in explaining cardiac dysfunction during the development of congestive heart failure (CHF), there are several conditions including initial stages of cardiac hypertrophy, where cardiac remodeling has also been found to be associated with either an increased or no change in heart function. Extensive studies have indicated that cardiac dysfunction is related to defects in one or more subcellular organelles such as myofibrils, sarcoplasmic reticulum and sarcolemma, depending upon the stage of CHF. Such subcellular abnormalities in the failing hearts have been shown to occur at both genetic and protein levels. Blockade of the renin-angiotensin system has been reported to partially attenuate changes in subcellular protein, gene expression, functional activities and cardiac performance in CHF. These observations provide support for the role of subcellular remodeling (alterations in molecular and biochemical composition of subcellular organelles) in cardiac dysfunction in the failing heart. On the basis of existing knowledge, it appears that subcellular remodeling during the process of cardiac remodeling plays a major role in the development of cardiac dysfunction in CHF.

Cardiac remodelling: General aspects and mechanisms

“…In physiological conditions, the excitation-contraction process is activated after a small quantity of Ca 2+ influx through SL, which in turn stimulates a release of Ca 2+ from the SR. In the relaxation phase, it is estimated that approximately 80% of the free cytoplasmic Ca 2+ is accumulated in the SR (45). In cardiac remodelling, modifications in the expression of the saarcolemmal Na + Ca 2+ exchanger (which uses the influx of Na + to remove the intracellular Ca 2+ ) and the SR Ca 2+ -ATPase (SERCA) (which is responsible for Ca 2+ sequestration during diastolic phase) have been reported (46).…”

Oxidative stress and ischemia-modified albumin in chronic ischemic heart failure

“…The most common causes of HF are coronary heart disease, hypertension, cardiomyopathy, valvular heart disease, and type 2 diabetes mellitus. 1 The high prevalence of cardiovascular diseases means that they are a constant focus of medical research. The role of oxidative stress in the development of cardiovascular injuries has been reliably established.…”

Isolation and Physiological Analysis of Mouse Cardiomyocytes

“…Changes in any or all of these cell types can be seen in heart failure, making determination of the ultimate cause of heart dysfunction difficult. Decreased ventricular contractility of a failing heart is preceded by varying degrees of fibrous tissue build-up and hypertrophy and dysfunction of the cardiomyocytes 1 . Arrhythmias can be caused by dysfunction in the conducting cells 2 , fibrosis interrupting cardiac conduction 3 , or changes in the expression of ion channels in cardiomyocytes 1,4 .…”