肾素(前体)受体系统致人静脉内皮细胞损伤机制的研究的中期报告.docxVIP

肾素(前体)受体系统致人静脉内皮细胞损伤机制的研究的中期报告 Introduction: The renin-angiotensin-aldosterone system (RAAS) plays a critical role in regulating blood pressure and fluid-electrolyte balance. Angiotensin II (Ang II), the primary effector peptide of the RAAS, exerts its physiological effects by binding to specific receptors, with type 1 (AT1R) and type 2 (AT2R) receptors being the most widely studied. AT1R activation is associated with vasoconstriction, sodium retention, and oxidative stress, whereas AT2R activation is generally thought to exert cardiovascular and renal protective effects. However, recent studies have revealed a novel pathway involving the prorenin/renin receptor (PRR), which is a component of the RAAS that acts independently of Ang II. The PRR is expressed in various tissues, including the vascular endothelium, where it mediates the activation of various intracellular signaling pathways. Objective: The objective of this study is to investigate the mechanisms underlying the damaging effects of PRR activation in human endothelial cells and to determine whether this pathway contributes to the pathogenesis of cardiovascular disease. Materials and methods: Human umbilical vein endothelial cells (HUVECs) were incubated with recombinant human prorenin in the absence or presence of PRR antagonists, AT1R antagonists, or AT2R antagonists. The cells were then analyzed for markers of endothelial cell damage, including reactive oxygen species (ROS) production, apoptosis, and mitochondrial dysfunction. Additionally, the expression of various markers of endothelial cell activation and inflammation was assessed using real-time PCR and ELISA assays. Results: Our results demonstrate that prorenin induces oxidative stress and mitochondrial dysfunction in HUVECs, leading to apoptosis and cellular damage. Furthermore, we found that PRR antagonist treatment significantly attenuated these effects, suggesting that PRR activation is a key mediator of prorenin-induced damage. Interestingly,