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

前期项目的结果证实了在CRU342第一期资助期内，谷氨酰胺治疗对心脏手术后肾损伤的保护作用（临床研究），以及对肾缺血-再灌注模型小鼠模型AKI的发展有保护作用。在AKI疾病模型中，分子成像显示这种效应与谷氨酰胺消耗增加无关。此外，临床研究和初步实验的其他结果表明，血管紧张素II可以通过调节肾脏的微血流动力学和肾小球滤过以及炎症反应来改善AKI的发展。因此，这个新项目将研究血管紧张素II对心脏手术患者肾脏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迹的分子机制和影响将通过多尺度和翻译成像方法进行研究，包括活体显微镜、功能/代谢和新的AT1受体靶向全身成像，并将建立和应用于关联区域肾脏灌注、功能和炎症。和AT受体密度在疾病自发过程中，以及在疾病模型和最终在患者中进行血管紧张素ii靶向干预后。

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.