Uremia and Cardiac Remodelling -Role of the Renin-Angiotensin-System in the Pathogenesis and Progression of the Cardiorenal Syndrome

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Cardiovascular complications due to accelerated atherosclerosis are the main cause of morbidity and mortality in patients with chronic kidney diseases. This high risk population has a 3 to 50-times higher cardiovascular mortality even before they reach the stage of terminal renal failure, and the relationship is often described as the cardio-renal syndrome. The common pathophysiologic pathway is thought to be a perpetuating injury to the vascular system. The aim of the present project is to expand our knowledge on pivotal pathophysiologic mechanisms related to vascular injury in the presence of combined heart and kidney failure in a newly designed experimental model of combined aortic banding and 5/6 nephrectomy. In this model particular focus will be placed on the role of the renin-angiotensin-system (RAS), and the mediation of inflammation, endothelial dysfunction und hampered endothelialvascular regeneration that results from RAS activation. For this purpose we will evaluate two animal strains with different renin gene expression and hence different plasma and tissue renin activity. The results should provide new integrative therapeutic options in patients with cardiac and renal dysfunction.