Regulation of hypertrophy and atrophy in cultured adult heart cells.

Abstract

Mechanical loading and alpha-adrenergic receptor stimulation have both been shown to induce hypertrophy in isolated neonatal heart cells. The present study examined the effects of adrenergic hormones and contractile activity on the hypertrophic response in isolated adult feline cardiomyocytes maintained for more than 14 days in insulin- and serum-supplemented medium. Measurements of the hypertrophic response included cell size, total protein content, myosin heavy chain content, and the time course of activation of increased protein synthesis. Reactivation of the "fetal" gene program was evaluated by secretion of atrial natriuretic factor (ANF) into the medium. Significant myocyte hypertrophy was induced in both quiescent myocytes treated with alpha 1-adrenergic agonists and in beating myocytes treated with beta-adrenergic agonists. However, there were both quantitative and qualitative differences in the response to each type of stimulation. alpha-Adrenergic agonists promoted an increase in cell size, protein content, and ANF secretion but not myofibrillar reorganization, which was observed only in beating myocytes. In contrast to results reported for neonatal heart cells, determinants of hypertrophy in beating myocytes exceeded those in nonbeating alpha 1-adrenergic agonist-treated heart cells in every parameter examined. In addition, in the case of both beating and alpha-adrenergic stimulation, there were marked time-dependent variations in rates of protein synthesis over the interval of 4 hours to 7 days of treatment with each type of stimulus. Differences were also encountered in correlations between rates of protein synthesis and protein accumulation over this interval. The effect of beating was particularly important both to the reorganization of myofibrillar structure and the metabolism of myosin heavy chain. In cultures in which beating was inhibited with the calcium channel antagonist nifedipine, the loss of myosin heavy chain was significantly greater than that of total protein.

Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

“…These papers were the first demonstration that catecholamines induce cardiac myocyte hypertrophy directly. This finding was later confirmed in cultured adult rat and cat cardiac myocytes (Simpson, 1988;Fuller et al, 1990;Ikeda et al, 1991;Volz et al, 1991;Clark et al, 1993).…”

β-Adrenergic receptor stimulation induces endoplasmic reticulum stress in adult cardiac myocytes: role in apoptosis

“…In neonatal rat cardiac myocytes, antibodies against β1-AR induced ER stress and apoptosis [18]. Neonatal and adult cardiac myocytes are suggested to be physiologically different with respect to growth/hypertrophy and adrenergic physiology [36–38]. Here, we provide evidence that pharmacological inducers of ER stress (thapsigargin and brefeldin A) induce apoptosis in adult cardiac myocytes.…”

Contraction Accelerates Myosin Heavy Chain Synthesis Rates in Adult Cardiocytes by an Increase in the Rate of Translational Initiation

“…The adult cardiocytes were cultured and maintained in a two-dimensional tissue culture environment and were not mechanically loaded to the same extent as cardiocytes in vivo. In addition, cultures of adult feline cardiocytes in serum-free medium have a slightly decreased rate of protein synthesis as compared with cells maintained in medium supplemented with serum (37). These lower rates may reflect an overall decreased translational efficiency and in part account for the relatively high percentage of MHC mRNA in the mRNP fraction.…”