Loirand Gervaise, Scalbert Elizabeth, Bril Antoine, Pacaud Pierre
Inserm, U915, Nantes F-44000, France.
Curr Opin Pharmacol. 2008 Apr;8(2):174-80. doi: 10.1016/j.coph.2007.12.006. Epub 2008 Jan 28.
Increasing evidence has accumulated to implicate overactivation of Rho protein as a common component for the pathogenesis of several cardiovascular disorders including hypertension, coronary and cerebral vasospasm, atherosclerosis, and diabetes. Recent advances in Rho protein signaling research indicate that the Rho exchange factors (Rho GEFs) which activate Rho proteins by catalyzing the exchange of GDP for GTP are major regulators of Rho protein activity. In addition, linkage analysis and association studies have recently identified Rho GEFs as susceptibility genes for cardiovascular diseases. All of these data are converging to suggest that as upstream activators of Rho proteins, Rho GEFs expressed in cardiovascular cells are good candidate targets for the treatment of cardiovascular disorders.
越来越多的证据表明，Rho蛋白过度激活是包括高血压、冠状动脉和脑血管痉挛、动脉粥样硬化以及糖尿病在内的多种心血管疾病发病机制的共同组成部分。Rho蛋白信号研究的最新进展表明，通过催化GDP与GTP交换来激活Rho蛋白的Rho交换因子（Rho GEFs）是Rho蛋白活性的主要调节因子。此外，连锁分析和关联研究最近已将Rho GEFs确定为心血管疾病的易感基因。所有这些数据都表明，作为Rho蛋白的上游激活剂，心血管细胞中表达的Rho GEFs是治疗心血管疾病的良好候选靶点。
