9410209 Cezeaux This Research Initiation Award proposes the study of the effects of mechanical stretch and the renin-angiotensin- aldosterone system on cardiac myocytes and non-myocytes in ventricular wall remodeling in cardiac hypertrophy. Of particular interest is the hyperplasia response of non- myocytes in response to angiotensin II produced locally by non-myocytes and by myocytes. A component of nonmyocytes hyperplasia can be increased collagen synthesis which may be modulated by aldosterone. It is hypothesized that stretch induces an increase in production of angiotensin II in both myocytes and non-myocytes and that angiotensin II causes nonmyocyte hyperplasia by paracrine and autocrine pathways. Using a mechanical stretching device to apply uniaxial stretch to cultured cardiac cells to simulate ventricular pressure overload, cells will be stretched at 10% and 20% for 24 hours. Modulation of renin and angiotensin II levels in response to stretch will be determined by measuring renin mRNA by RT-PCR and angiotensin II productions by radioimmunoassay. It is expected that this study will advance the knowledge of the response of cardiac cells to various stimuli, an important factor in tissue engineering in the cardiovascular system. ***
