Regulation of protein synthesis and degradation in adult ventricular cardiomyocytes

Abstract

For studies on the regulation of myocardial protein metabolism, isolated adult cardiomyocytes were introduced as an experimental model about a decade ago. When used shortly after isolation, this model represents a tool for studying the properties of normal and diseased myocardium on the cellular level. The influence of various peptide hormones, neurotransmitters, and mechanical stimulation on protein synthesis and degradation in isolated cardiomyocytes has been studied. It has been demonstrated, for example, that alpha 1-adrenoceptor stimulation increases protein synthesis in newly isolated cardiomyocytes, independently of any mechanical effects. Other potential growth stimuli require appropriate conditions to induce cellular responsiveness. Neuropeptide Y, for example, does not stimulate cellular protein synthesis in newly isolated cells, whereas it does so in cells that have been cultured for a week in the presence of serum. Mechanical stretch also represents a growth stimulant. It seems that its signal transduction involves an autocrine loop. Thus different mechanisms, by which exogenous influences can modify cellular protein synthesis and degradation, have been identified on the cellular level, with the use of isolated adult cardiomyocytes.

Plasma Parathyroid Hormone and the Risk of Cardiovascular Mortality in the Community

“…6,29,30 Second, PTH appears also to have detrimental effects on the myocardium via induction of left ventricular hypertrophy, cardiac calcification, and fibrosis. 5,9,[31][32][33] Third, higher PTH is associated with both established cardiovascular risk factors 8,34 and more recently described risk factors such as inflammation markers, 35 renal dysfunction, 36 and cardiac pathology. 2,35,37 The fact that PTH remained significantly associated with CVD mortality in all multivariable models suggests that confounding by these factors is not the sole explanation for our findings.…”

Plasma–Parathyroid Hormone Is Associated With Subclinical and Clinical Atherosclerotic Disease in 2 Community-Based Cohorts

“…5,6,18,19 Second, PTH seems to be involved in diseases of the myocardium via induction of left ventricular hypertrophy, congestive heart failure, cardiac calcification and fibrosis, detrimental states that all have secondary negative effects on the vasculature. 8,[24][25][26][27] Third, higher PTH is associated with both established cardiovascular risk factors 28,29 and more recently described risk factors such as markers of inflammation, renal dysfunction, and cardiac pathology. 8,30,31 The fact that PTH was consistently associated with atherosclerotic disease and death in all multivariable models suggests that confounding by these other factors is not the sole explanation for our findings.…”

Predominant activation of endothelin-dependent cardiac hypertrophy by norepinephrine in rat left ventricle

“…This is particularly interesting from a pathogenic point of view, as several studies suggest that ET-1 may act as a "triggering factor" for myocardial growth (12,15,21). Isolated cardiac myocytes display a hypertrophic response with ␣-adrenergic stimulation (30,31), and it has recently been shown that the ␣ 1 -adrenoreceptor agonist phenylephrine induces ET-1 gene expression and accelerates the conversion of big ET to bioactive ET-1 in cultured neonatal cardiomyocytes (14). Stimulation of the cardiac ET system with adrenergic activation therefore appears to constitute an important signaling pathway of early myocardial growth, which may initiate cardiomyocyte hypertrophy even in pathophysiological states without obvious catecholamine excess such as renal artery stenosis (7).…”