The Renin-Angiotensin II Axis: a Novel Target for the Treatment of Acute Kidney Injury

先前项目的结果证明了在CRU 342的第一个资助期内，谷氨酰胺治疗性给药对心脏手术后肾损伤（临床研究）和肾缺血-再灌注模型后小鼠模型中阿基发展的保护作用。使用分子成像显示，这种作用与阿基疾病模型中谷氨酰胺消耗增加无关。此外，来自临床研究和初步实验的额外结果已经导致以下假设：血管紧张素II给药可以通过调节微血流动力学和肾小球滤过以及肾脏中的炎症反应来改善阿基的发展。因此，这个新项目将研究血管紧张素II给药对心脏手术患者队列中肾损伤和炎症特征的影响。血管紧张素II对转录组和蛋白质组印记的分子机制和作用将通过使用从活体显微镜到功能/代谢的多尺度和平移成像方法进行研究，并将建立新的AT 1受体靶向全身成像并应用于关联区域肾脏灌注，功能和炎症，和AT受体密度在疾病的自发过程中和血管紧张素II靶向干预后的疾病模型，并最终在患者。

The results from the previous project demonstrated the protective effect of the therapeutic administration of glutamine on kidney damage after cardiac surgery (clinical study) and on AKI development in a murine model after renal ischemia-reperfusion model during the first funding period of the CRU342. Using molecular imaging it was shown that this effect is not associated with enhanced glutamine consumption in AKI disease models. Furthermore, additional results from clinical studies and preliminary experiments have led to the hypothesis that angiotensin II administration may ameliorate the development of AKI by modulating both the regulation of the microhemodynamics and the glomerular filtration as well as the inflammatory response in the kidney. Thus, this new project will investigate the effect of angiotensin II administration on kidney damage and the inflammatory signature in a cohort of cardiac surgery patients. The molecular mechanism and the effect of angiotensin II on transcriptomic and proteomic imprinting will be investigate by using multiscale and translational imaging approaches ranging from intravital microscopy to functional/metabolic and novel AT1 receptor-targeted whole-body imaging will be established and applied to correlate regional kidney perfusion, function and inflammation, and AT receptor density during the spontaneous course of the disease and following angiotensin II-targeted interventions in disease models and finally in patients.