Cardiac remodeling and subcellular defects in heart failure due to myocardial infarction and aging

Abstract

Although several risk factors including hypertension, cardiac hypertrophy, coronary artery disease, and diabetes are known to result in heart failure, elderly subjects are more susceptible to myocardial infarction and more likely to develop heart failure. This article is intended to discuss that cardiac dysfunction in hearts failing due to myocardial infarction and aging is associated with cardiac remodeling and defects in the subcellular organelles such as sarcolemma (SL), sarcoplasmic reticulum (SR), and myofibrils. Despite some differences in the pattern of heart failure due to myocardial infarction and aging with respect to their etiology and sequence of events, evidence has been presented to show that subcellular remodeling plays a critical role in the occurrence of intracellular Ca(2+)-overload and development of cardiac dysfunction in both types of failing heart. In particular, alterations in gene expression for SL and SR proteins induce Ca(2+)-handling abnormalities in cardiomyocytes, whereas those for myofibrillar proteins impair the interaction of Ca(2+) with myofibrils in hearts failing due to myocardial infarction and aging. In addition, different phosphorylation mechanisms, which regulate the activities of Ca(2+)-cycling proteins in SL and SR membranes as well as Ca(2+)-binding proteins in myofibrils, become defective in the failing heart. Accordingly, it is suggested that subcellular remodeling involving defects in Ca(2+)-handling and Ca(2+)-binding proteins as well as their regulatory mechanisms is intimately associated with cardiac remodeling and heart failure due to myocardial infarction and aging.

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

“…due to reduced glomerular filtration rate), or by the combined action of these two mechanisms. Indeed, as recently shown in detail [43,44], several age-associated disorders can cause the death of cardiomyocytes, with the consequent release of sarcolemma proteins, including cTnI and cTnT. On the other hand, circulating cTnI and cTnT are fragmented into molecules small enough to be cleared by the kidney of healthy subjects [45].…”

Reversal of Cardiac Remodeling and Subcellular Defects by Prazosin in Heart Failure Due to Myocardial Infarction

“…Cardiac dysfunction in heart failure is invariably explained on the basis of changes in shape and size of the heart (cardiac remodeling) [22] as well as defects in subcellular organelles such as Sarcoplasmic Reticulum (SR) and Myofibrils (MF) [23][24][25]. Since the sympathetic nervous system is markedly activated in heart failure [26,27], the elevated levels of plasma catecholamines are known to play a critical role in the pathogenesis of cardiac dysfunction, cardiac remodelingmediated through the participation of both α-AR and β-AR in the myocardium.…”

“…This study was therefore undertaken to investigate if the depressed cardiac function in rats with heart failure due to MI is improved and cardiac remodeling is attenuated upon treatment with prazosin, a well-known α-AR blocker. Since both SR and MF are intimately involved in determining the status of cardiac contraction and relaxation [23][24][25] -stimulated ATPase were examined in MI animals with or without prazosin treatment. Furthermore, to test if the beneficial effects of α-AR blockade on subcellular activities occur at the level of cardiac gene expression [23][24][25], changes in mRNA levels for both SR and MF proteins were measured in untreated and prazosin treated hearts.…”

“…Since both SR and MF are intimately involved in determining the status of cardiac contraction and relaxation [23][24][25] -stimulated ATPase were examined in MI animals with or without prazosin treatment. Furthermore, to test if the beneficial effects of α-AR blockade on subcellular activities occur at the level of cardiac gene expression [23][24][25], changes in mRNA levels for both SR and MF proteins were measured in untreated and prazosin treated hearts. Because of the involvement of sympathetic nervous system activation and subsequent elevated levels of plasma catecholamines in heart failure [26,27], the status of plasma NE, Epinephrine (EPI) and dopamine in MI-induced heart failure was monitored upon treatment with prazosin.…”

Dynamic Alterations in the CaV1.2/CaM/CaMKII Signaling Pathway in the Left Ventricular Myocardium of Ischemic Rat Hearts

“…An increase in cytoplasmic Ca 2 + concentration in myocardial cells with hypoxia has been reported (Song et al, 2005;Liu et al, 2009), and intracellular Ca 2 + overload is an important cause for damage and dysfunction in the myocardium (Tang et al, 2011;Dhalla et al, 2012). As Ca V 1.2 is involved in the major route for Ca 2 + to enter into myocardial cells, the decreased expression of Ca V 1.2 and the overload of intracellular Ca 2 + seemed to be paradoxical, which suggests that intracellular Ca 2 + overload of MI may be related to other regulatory proteins of Ca V 1.2, such as Na + /Ca 2 + exchanger, Na + /H + exchanger, RyR, and SER-CA (Zima and Blatter, 2006;Vittone et al, 2008).…”