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

动脉粥样硬化加速引起的心血管并发症是慢性肾病患者发病和死亡的主要原因。这些高危人群甚至在达到终末期肾衰竭阶段之前，心血管死亡率就高出3到50倍，这种关系通常被描述为心肾综合征。常见的病理生理途径被认为是对血管系统的永久性损伤。本项目的目的是在一个新设计的联合主动脉束带和5/6肾切除术的实验模型中，扩大我们对合并心衰和肾衰竭时血管损伤相关的关键病理生理机制的认识。在这个模型中，特别关注肾素-血管紧张素系统（RAS）的作用，以及RAS激活导致的炎症、内皮功能障碍和内皮血管再生受阻的中介作用。为此，我们将评估两种不同肾素基因表达的动物菌株，从而评估不同的血浆和组织肾素活性。该结果将为心功能障碍和肾功能障碍患者提供新的综合治疗选择。

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.