CRP促进eNOS聚集于内皮细胞膜而失活导致高血压的机制研究

C反应蛋白(C-reactive protein，CRP)是血管功能紊乱及高血压最重要的炎症标记物，但其能否致病仍有争议。我们最近发现临床浓度的CRP(3-15mg/l)可导致大鼠高血压、血管舒张功能下降、NO释放减少，长期可引起心脏肥厚合并心肌纤维化，此作用在eNOS敲除小鼠消失，且CRP使得caveolin-1及eNOS聚集于内皮细胞膜，致eNOS失活，推测人CRP可通过caveolin-1使得eNOS失活与细胞膜导致高血压。本课题拟在前期研究的基础上， 多种方式（转基因、腺病毒、蛋白注射）给予CRP，明确hCRP对血压及内皮功能的调节作用，从分子（受体-caveolin-eNOS）、细胞（内皮特异性Cre-Flox）、整体（血压及内皮功能）探索人CRP引起高血压及其具体机制，为临床高血压防治提供新的分子细胞学依据。

C-reactive protein (CRP) is the most important inflammatory marker in vascular dysfunction and hypertension, but whether it is a marker or a pathogenic factor is still controversial. We recently found that clinical concentration CRP (3-15mg/l) induce spontaneous hypertension, reduced endothelial-dependent vasodilation, cardiac hypertrophy, myocardial fibrosis. CRP lost these function in eNOS knockout mice. Moreover, CRP induces caveolin-1 and eNOS accumulation on endothelial cell membrane, then induces eNOS dysfunction. Then, we speculated that human CRP can cause hypertension througth the caveolin-1-eNOS pathway. Therefore, on the basis of previous studies，this subject using a variety of ways (transgenic rats, adeno-associated virus, CRP direct injection) to give human CRP administration, detecting blood pressure and endothelial function, exploring human CRP-induced hypertension and its specific mechanisms from the perspective of molecular (caveolin-1-eNOS), cells (endothelial specific Cre-Flox) and in vivo (blood pressure and endothelial function). It provides a new molecular cytological basis for solving the controversy of human CRP-induced hypertension and clinical treatment of hypertension.