Study On The Role And Immune Mechanism Of Valsartan Attenuates Atherosclerosis In Prolonged Exogenous Angiotensin â…¡-treated ApoE-/-Mice

Part I. A study of plaque stability of exogenous angiotensin II-treated ApoE-/-mice administrated with valsartanObjective:To study the plaque stability of exogenous angiotensin II-treated ApoE-/-mice administrated with valsartan.Methods:ApoE-/-mice were divided into three groups:control groups (group I), exogenous angiotensin II-treated groups (group II), and valsartan treated the groups II (group III). After exogenous Ang II treatment for8weeks, we detected the systolic blood pressure, heart rates, and serum lipid of the three groups, and we use the Oil-red staining to detected the area of the plaque on the root of aorta, use the immuohistochemistry technology to detected the a-sma and the masson staining to detected the collagen of the plaque on the root of aorta. We use the Real-Time RT-PCR and Western-blot to detected the gene and protein level expression of MMP-2and MMP-9of the whole blood vessel.Results:Compared with group I, the systolic blood pressure of Ang II treated-ApoE-/-mice were higher, and administrate the valsartan can reverse the blood pressure. There was no significant different among the three groups about the heart rates and serum lipid. Ang II treated mice had more area of AS plaque compared the control group, and the plaque was more vulnerable, but the valsartan group can reduce the plaque and made them more stability. The result of RT-PCR and Western blot about the expression of MMP-2and MMP-9was that group II had more expression of MMP-2and MMP-9compared group I, and administration with valsartan can attenuate the phenomenon.Conclusion:Administrated with valsartan can attenuate the progression of the Ang II treated ApoE-/-mice and make the plaque more stability. Part Ⅱ. A study of immune changes about exogenous angiotensin Ⅱ-treated ApoE-/-mice administrated with valsartan.Objective:Atherosclerosis is an immunology disease, and the mechanism of the immune changes can influence the stability of the plaque. Due to part Ⅰ have demonstrated that valsartan can reverse the vulnerable plaque of the Ang Ⅱ treated ApoE-/-mice, but the mechanism of the immune was unclear. So, this part is to study the immune changes of exogenous angiotensin Ⅱ-treated ApoE-/-mice treatment with valsartan.Methods:ApoE-/-mice were divided into three groups:control groups (group Ⅰ), exogenous angiotensin Ⅱ-treated groups (group Ⅱ), and valsartan treated the groups Ⅱ (group Ⅲ). After exogenous Ang Ⅱ treatment for8weeks, we use the flow cytometry to detect the changes of immune cells of the spleen of the mice. And we use ELISA to detect the serum cytokine of the mice. We use the immuohistochemistry technology to detect the moma and CD4+T cells of plaque on the aorta root.Results:The result of flow cytometry about the CD4+T cells was that Ang II can induce the effect of Thl and Thl7, but suppression the Th2and Tregs. However, administrate with valsartan can reverse the results, the frequency of Th2and Tregs were increased of group III, and decreased Thl and Thl7. The AngⅡ treated group can make the dendrite cells more maturity, but valsartan can reverse the phenomenon. The result of ELISA was that treated with Ang II can increase the Thl and Thl7cytokine profiles compared with control group, and administrated with valsartan can induce the cytokine profiles of Th2and Tregs compared with group II, and the results of RT-PCR have the same tendency of the ELISA.Conclusion:Administrated with valsartan can reverset the Ang II induced the imbalance of the immune response. And it’s the mechanism of the immune response to make the plaque more stability. Part III. A study of the role of IL-5on the anti-atherosclerotic process of exogenous angiotensin II-treated ApoE-/-mice administrated with valsartan.Objective:The process of anti-atherosclerotic when administrated with valsartan can induce the Th2response, especially to induce the secrete IL-5. So, this part use the anti-IL-5antibody to reduce the IL-5, and to observe the role of anti-atherosclerotic of valsartan.Methods:ApoE-/-mice were divided into two groups:valsartan treated Ang II-ApoE-/-mice and injected with rat-Ig G2a, another group is valsartan treated Ang II-ApoE-/-mice and injected with anti-IL-5antibody. We detected the systolic blood pressure of the two groups, the area and expression of inflammatory of the plaque on the aorta root.Results:The anti-IL-5antibody can aggravate the progression of the AS and have no effect on the blood pressure of the mice.Conclusion:Valsartan can induce the Th2response and increase the level of IL-5to play an anti-atherosclerotic role on the exogenous angiotensin Ⅱ-treated ApoE-/-mice.