Review Article
Renin-Angiotensin System, Hypertrophy and Gene Expression in Cardiac Myocytes

https://doi.org/10.1006/jmcc.1999.0934Get rights and content

Abstract

In response to humoral and mechanical stimuli, the myocardium adapts to increased work load through hypertrophy of individual muscle cells. Myocardial hypertrophy is characterized by an increase in cell size in the absence of cell division and is accompanied by changes in gene expression. Angiotensinii(ANGii), the effector peptide of the renin-angiotensin system (RAS), regulates volume and electrolyte homeostasis and is involved in cardiac and vascular growth in rats. In this review, the role of RAS on the myocyte protein synthesis (myocyte hypertrophy) and on the induction of gene expression will be discussed in rat cardiomyocytes in culture. The traditional RAS can be considered as a system in which circulating ANGiiis delivered to target tissues or cells. However, a local RAS has also been described in cardiac cells and evidence has been accumulated for autocrine and/or paracrine pathways by which biological actions of ANGiican be mediated. These actions of ANGiiare primarily mediated through ANGiireceptors of the subtypei(AT1-R). When evaluating the effects of ANGiiin situ, both changes in circulating levels and local production have to be taken into account. Discrepant findings on thein vitroeffect of ANGiion the protein synthesis in cardiac myocytes are described and can be at least partly be attributed to methodological problems such as assay of thede novoprotein synthesis, isolation and the separation procedure of cardiac myocytes. The ANGii-induced hypertrophic effect also depends on the existence of non-myocytes in a cardiocyte culture. In rat cardiocytes ANGiialso causes induction of many immediately-early genes (c-fos, c-jun, jun-B, Egr-1 and c-myc) and induces also late markers of cardiac hypertrophy (skeletalα-actin and atrial natriuretic peptide expression) and growth factors (TGF-β1gene expression).In vivoANGiivia AT1-R, causes not only ventricular hypertrophy, independently of blood pressure, but also a shift to the fetal phenotype of the myocardium. Angiotensin-converting enzyme inhibitors and ANGiireceptor antagonists of the subtypeinot only induce the regression, but also prevent the development of cardiac hypertrophy in experimental rat models.

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    Citation Excerpt :

    This remodeling of the heart is characterized by an altered phenotype and constitutes an independent risk factor for morbidity and mortality that usually leads to heart failure (Levy et al., 1990; Katholi and Couri, 2011). In this sense, chronic activation of the renin angiotensin system (RAS) is responsible for several cardiac diseases, among which myocardial hypertrophy occupies an outstanding place (Lijnen and Petrov, 1999). It is well documented that angiotensin II (ANGII) activates NADPH-oxidase increasing reactive oxygen species (ROS) production that play a crucial role in the development of CH(Garrido and Griendling, 2009; Zhang et al., 2013).

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Please address all correspondence to: Prof Dr P. Lijnen, Hypertension Unit, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.

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