Subcellular remodelling may induce cardiac dysfunction in congestive heart failure

Abstract

It is commonly held that cardiac remodelling, represented by changes in muscle mass, size, and shape of the heart, explains the progression of congestive heart failure (CHF). However, this concept does not provide any clear information regarding the development of cardiac dysfunction in CHF. Extensive research has revealed that various subcellular organelles such as the extracellular matrix, sarcolemma, sarcoplasmic reticulum, myofibrils, mitochondria, and nucleus undergo varying degrees of changes in their biochemical composition and molecular structure in CHF. This subcellular remodelling occurs due to alterations in cardiac gene expression as well as activation of different proteases and phospholipases in the failing hearts. Several mechanisms including increased ventricular wall stress, prolonged activation of the renin-angiotensin and sympathetic systems, and oxidative stress have been suggested to account for subcellular remodelling in CHF. Furthermore, subcellular remodelling is associated with changes in cardiomyocyte structure, cation homeostasis as well as functional activities of cation channels and transporters, receptor-mediated signal transduction, Ca(2+)-cycling proteins, contractile and regulatory proteins, and energy production during the development of heart failure. The existing evidence supports the view that subcellular remodelling may result in cardiac dysfunction and thus play a critical role in the transition of cardiac hypertrophy to heart failure.

Redox-Sensitive Endoplasmic Reticulum Stress and Autophagy at Rostral Ventrolateral Medulla Contribute to Hypertension in Spontaneously Hypertensive Rats

“…[10][11][12] Several recent studies have demonstrated that the redox-sensitive changes in biochemical compositions, as well as architecture and functions of subcellular organelles, including the mitochondria, 13 ER, 14 and nucleus, 15 underpin phenotypic trait of cardiovascular diseases. Of note is a recent demonstration 14 that oxidative stress causes ER stress, with subsequent activation of UPR, leading to tissue damage and manifestation of myocardial dysfunction.…”

Relação entre a esfericidade, a função ventricular e o tamanho do infarto em ratos

“…proceso resulta en mayor prevalencia de ruptura ventricular, aneurismas y arritmias malignas. Adicionalmente, la remodelación está relacionada a la aparición y la progresión de la disfunción ventricular [1][2][3][4][5][6][7] . Debemos tener en cuenta que una de las estrategias más utilizadas para el estudio de la remodelación resultante de la oclusión coronaria es el modelo del infarto experimental en el ratón.…”

“…Adicionalmente, la remodelación está relacionada a la aparición y la progresión de la disfunción ventricular [1][2][3][4][5][6][7] .…”

Role of intracellular Ca2+ overload in inducing changes in cardiac gene expression

“…Previous studies have revealed varying degrees of depression in gene expression for SL, SR and MF proteins, as well as defects in subcellular organelles during the development of heart failure in patients and experimental animal models (1)(2)(3)(4)(5)(6). Accordingly, it has been suggested that cardiac dysfunction in failing hearts is due to subcellular remodelling as a consequence of changes in cardiac gene expression (2,(7)(8)(9).…”