Th1, Th2, And Th17 Effector T Cells Response To Angiotensin Ⅱ And Carotid Atherosclerosis In Hypertensive Patients

PartⅠEvaluation of effector T cells activity related to angiotensinⅡin hypertensive patients with carotid atherosclerosisObjective:The goal of the present study was to elucidate the relationship between angiotensinⅡlevel and effector T cells (Th1, Th2 and Th17 cells) in hypertensive patients with carotid atherosclerosis.Methods:Forty-five hypertensive patients were divided into two groups by B-mode ultrasound inspection:group one consisting of 20 cases with carotid atherosclerosis (CA), and group two consisting of 25 cases without carotid atherosclerosis (EH). The control group consists of 20 health subjects without carotid atherosclerosis. Peripheral blood mononuclear cells were collected in a fasting state. The frequencies of Th1, Th2 and Th17 cells were analysed by flow cytometry. The levels of plasma angiotensinⅡwere measured by radioimmunoassay and IFN-γ, IL-4 and IL-17 were measured by ELISA. Moreover, quantitative real-time PCR was carried out to explore the mRNA expression of T-bet,GATA3 and RORyt.Results:Compared with these in EH and Control, the frequencies of Th1 and Th17 cells in CA were significantly increased, companied with a up-regulated expression of T-bet and RORyt mRNA and a higher level of IFN-γand IL-17. However, there was no significant difference in Th2 cells, GATA3 mRNA and IL-4 levels among these three groups. Moreover, Th1, Th17 cells, T-bet and RORyt mRNA and levels of IFN-γand IL-17 were no significant change in EH and Control. Furthermore, the levels of angiotensin II in CA were significantly higher than those in EH and Control, indicating that the levels of angiotensinⅡwere positively correlated with the levels of IFN-γ, IL-17, Th1 and Th17 cells, and were not correlated with the levels of IL-4 and Th2 cells.Conclusion:Results collectively suggest that the changes of angiotensinⅡ, Th1 and Th17 cells in hypertensive patients probably contribute to the development of carotid atherosclerosis.PartⅡAngiotensinⅡup-regulates effector T cells activityObjective:The goal of the present study was to explore the effect of angiotensinⅡon Th1, Th2 and Th17 cells activity.Methods:Blood was obtained from 8 health subjects in a fasting state. The peripheral blood mononuclear cells were cultured and stimulated with angiotensinⅡ(0.01 to 1μmol/L), with and without pretreatment with 1μmol/L valsartan. After 48 hours, flow cytometry was used to measure the frequencies of Th1, Th2 and Th17 cells, ELISA was used to measure the levels of IFN-γ, IL-4 and IL-17 and quantitative real-time PCR was carried out to explore the mRNA expression of T-bet, GAT A3 and RORyt.Results:After stimulated with angiotensinⅡ, the frequencies of Th1 and Th17 cells were significantly increased, the expression of T-bet and RORyt mRNA was enhanced, and the levels of IFN-γand IL-17 were dose-dependently increased. In addition,these AngⅡdose-dependent effect was blocked by pretreatment with valsartan. However, there was no significant difference in Th2 cells, GATA3 mRNA and IL-4 levels among these samples. Conclusions:Results collectively suggest that angiotensinⅡmay up-regulate the activity of Th1 and Th17 cells, which may contribute to the initiation and progression of atherosclerosis in hypertensive patients. Moreover, valsartan could reverse angiotensin II's up-regulation on effector T cells, which may be a mechanism of the anti-atherosclerosis effect of valsartan.