Rho GDI通过T淋巴细胞调节高血压发生的病理生理机制

T lymphocytes play a critical role in the development of hypertension. Rho GDI, an important negative regulator of Rho signaling pathway, involves in a variety of cardiovascular diseases induced by inflammation. While the role of Rho GDI in the genesis and development of hypertension is still unclear.Our previous study found that the expression of Rho GDIβ was downregulated and Rho was upregulated in T lymphocytes of blood vessel in angiotensin II (Ang II)-induced hypertension, and the blood pressure of Rho GDIβ transgenic mice was elevated significantly. But whether Rho GDI is invovled in the regulation of hypertension induced by T lymphocytes is still unknown. In this study, we will use Rho GDIβ transgenic mice and co-culture system of T lymphocytes with endothelial cells or smooth muscle cells in vitro in Ang II induced hypertension model to investigate the mechanism of Rho GDI on proliferation and activation of T lymphocytes, the mechanism of Rho GDI of T lymphocytes on apoptosis, proliferation and transformation of endothelial cells and smooth muscle cells, the mechanism of Rho GDI on vascular relaxation and hypertension genesis. The above study will provide an important basis for elucidating the pathophysiological mechanism of hypertension and finding novel anti-hypertensive drug targets.

T淋巴细胞在高血压发生中起着重要的作用。Rho GDI是Rho信号通路重要的负性调控因子，参与多种炎症相关的心血管疾病，但其在高血压中的作用尚不清楚。我们前期研究发现，在血管紧张素II（Ang II）诱导的高血压小鼠模型中，血管中T淋巴细胞的Rho GDIβ表达明显下调，而Rho表达上调；Rho GDIβ转基因小鼠可显著降低Ang II诱导的血压升高。但是Rho GDI是否通过T淋巴细胞调控高血压的发生仍需要深入研究。本课题拟应用Rho GDIβ转基因小鼠及体外细胞（T淋巴细胞、内皮和平滑肌细胞）共培养体系，在Ang II诱导的高血压模型中，探讨Rho GDI调节T淋巴细胞增殖和活化的机理；研究T淋巴细胞Rho GDI调节内皮细胞凋亡、平滑肌细胞增殖和转化的机制；明确Rho GDI调节血管舒张功能和高血压发生的病理生理机制。为阐明高血压的病理生理机制及寻找抗高血压新药靶点提供重要依据。

T淋巴细胞在高血压发生中起着重要的作用。Rho GDI是Rho信号通路重要的负性调控因子，参与多种炎症相关的心血管疾病，但其在高血压中的作用尚不清楚。我们前期研究发现，在血管紧张素II（Ang II）诱导的高血压小鼠模型中，血管中T淋巴细胞的Rho GDIβ表达明显下调，而Rho表达上调；Rho GDIβ转基因小鼠可显著降低Ang II诱导的血压升高。但是Rho GDI是否通过T淋巴细胞调控高血压的发生仍需要深入研究。本课题拟应用Rho GDIβ转基因小鼠及体外细胞（T淋巴细胞、内皮和平滑肌细胞）共培养体系，在Ang II诱导的高血压模型中，探讨Rho GDI调节T淋巴细胞增殖和活化的机理；研究T淋巴细胞Rho GDI调节内皮细胞凋亡、平滑肌细胞增殖和分化的机制；明确Rho GDI调节血管舒张功能和高血压发生的病理生理机制。为阐明高血压的病理生理机制及寻找抗高血压新药靶点提供重要依据。