Neurohormonal regulation of myocardial cell apoptosis during the development of heart failure

Abstract

Adult cardiac myocytes are terminally differentiated cells that are no longer able to divide. Accumulating data support the idea that apoptosis in these cells is involved in the transition from cardiac compensation to decompensated heart failure. Since a number of neurohormonal factors are activated in this state, these factors may be involved in the positive and negative regulation of apoptosis in cardiac myocytes. beta1-Adrenergic receptor and angiotensin type 1 receptor pathways, nitric oxide and natriuretic peptides are involved in the induction of apoptosis in these cells, while alpha1- and beta2-adrenergic receptor and endothelin-1 type A receptor pathways and gp130-related cytokines are antiapoptotic. The myocardial protection of the latter is mediated, at least in part, through mitogen-activated protein kinase-dependent pathways, compatible with the findings in other cell types. In contrast, signaling pathways leading to apoptosis in cardiac myocytes are distinct from those in other cell types. The cAMP/PKA pathway induces apoptosis in cardiac myocytes and blocks apoptosis in other cell types. The p300 protein, a coactivator of p53, mediates apoptosis in fibroblasts but appears to play a protective role in differentiated cardiac myocytes. The inhibition of myocardial cell apoptosis in heart failure may be achieved by directly blocking apoptosis signaling pathways or by modulating neurohormonal factors involved in their regulation. These may provide novel therapeutic strategies in some forms of heart failure.

GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure

“…The activations of sympathoadrenal and renin-angiotensin systems are important factors in the development of heart failure (7,31,36). NE and ANG II increase peripheral arterial resistance and stimulate myocardial hypertrophy and apoptosis, thereby worsening cardiac performance (16,18). NE has been found to desensitize the myocardial ␤-adrenoceptor, thereby impairing the cardiac response to CA (22).…”

Cardiomyocyte Apoptotic Cell Death in Arterial Hypertension

“…Briefly, recent works indicate that the p38␣ isoform facilitates apoptosis, whereas the p38␤ isoform mediates a hypertrophic response, 36 and the p300-related proteins are involved in cardiomyocyte specific survival. 37 The precise role of these and other molecular pathways in the development of cardiomyocyte apoptosis present in hypertensive remodeling requires further investigation.…”

Association of depressed cardiac gp130-mediated antiapoptotic pathways with stimulated cardiomyocyte apoptosis in hypertensive patients with heart failure

“…Mechanical and humoral factors that are stimulated in heart-failure patients may induce the apoptotic process in cardiomyocytes [4]. Alternatively, apoptosis may reflect abnormalities in some factors that act within the cardiomyocyte, determining its resistance to apoptosis; that is, the glycoprotein 130 (gp130)-mediated survival pathway.…”