Adrenergic hormones and control of cardiac myocyte growth

Abstract

The molecular mechanisms of cardiac myocyte growth are relevant to important problems in cardiovascular disease. A cell culture model has been developed to explore the role of adrenergic hormones in cardiac myocyte growth and gene expression. Activation of a cardiac myocyte alpha 1-adrenergic receptor by catecholamines induces hypertrophic growth of neonatal rat cardiac myocytes and initiates selective increases in contractile protein gene transcription. These effects on growth and gene expression do not depend on contractile activity. The cardiac myocytes contain at least two subtypes of alpha 1-adrenergic receptors and at least three isoforms of protein kinase C (PKC). A distinct alpha 1 receptor subtype may mediate hypertrophy and gene transcription. Different isoforms of PKC are translocated to different intracellular sites on activation, and there is evidence that the beta-PKC isoform may be an element in the signal transduction pathway from an alpha 1 receptor at the surface to the cardiac myocyte nucleus. Growth regulation through a beta-adrenergic receptor can also be demonstrated in the culture model. The growth response mediated through a beta-adrenergic receptor differs in several respects from that transduced through an alpha 1-adrenergic receptor.