The Roles Of Th17 Cells In Atherosclerosis And The Effects Of All-trans-retinoic- Acid On This Process

Objective To investigate the roles of T help 17 cells in atherosclerosis(AS)and to study the effects of ATRA on this process. Methods In the first part of experiment ,the participants in the study were patients with chest pain syndrome (CPS), stable angina (SA), unstable angina(UA), acute myocardial infarction(AMI). The frequencies of Th17 in peripheral blood, the serum levels of IL-17 and ox-LDL, and the levels of RORγt were measured by FCM, ELISA, and RT-PCR respectively. The frequencies of Th17 in peripheral blood of patients with CPS were measured by FCM after being stimulated with ox-LDL at different concentrations for 24 hours and 48 hours.FCM were used to measure the effects of ATRA on expression of Th17 cells treated with ox-LDL in patients of 4 groups. Naive T cells were separated from CPS and cultured in vitro. Cytokines IL-1β, IL-6 ,IL-23were used to induce naive T cells to develop into Th17 cells, the effects of ATRA and ox-LDL on development of Th17 cells were study.In the second part of experiment,immune injury and high-fat feeding being used to establish a rat AS model. 30 Sprague Dawley rats were randomly divided into 5 groups: normal group, high-cholesterol group, immune-injured group, high-cholesterol and immune-injured group, ATRA group.Serum cholesterol were analyzed. HE stain were applied to observe organizational changes in aorta, and FCM to test the frequencies of Th17 in peripheral blood. Results The ratios of CD4+IL17+/CD4+T cells in ACS patients were significantly higher than those in SA and CPS, and there was also obvious differences between the SA and CPS groups. Levels of IL-17, ox-LDL and RORγt in patients with ACS increased significantly compared with patients with SA and CPS. In vitro incubation of peripheral blood mononuclear cells from CPS patients with ox-LDL resulted in a significant elevation of Th17 cells in a dose-and time-dependant manner. Th17 cells from ACS patients were significantly more susceptible to ox-LDL -mediated alterations. ATRA reduced the elevation of Th17 cells treated with ox-LDL in four groups. ATRA inhibited the effects of IL-1β. , IL-6 ,IL-23 on differentiation of Th17 cells .But there have no significant effects on differentiation of Th17 cells treated with ox-LDL.The cholesterol in serum of the high-cholesterol groups,the high-cholesterol and immune-injured groups increased significantly compared with normal groups and immune-injured groups(P<0.05), but the levels of cholesterol did not differ significantly between ATRA and other groups.The HE staining indicated that there are edematous thickening of the intima with deposition of a large number of foam cells and a mild atrophy in the membrane in the high-cholesterol and immune-injured groups,there was a less extent on pathological changes in immune-injured groups and ATRA groups.Compared with normal groups and high-cholesterol groups ,the frequencies of Th17 cells were significiantly increased in immune-injured groups and high-cholesterol and immune-injured groups(P<0.05). The frequencies of Th17 cells in ATRA groups were significiantly decreased compared with high-cholesterol and immune-injured groups (P<0.05).Conclusion The levels of Th17,IL-17,ox-LDL and RORγt increased obviously in patients with ACS.Th17 may play a potential role in the progression and stability of atheroma. Ox-LDL could promote the levels of Th17 while ATRA inhibit this effect. ATRA could inhibits but ox-LDL have no significant effects on differitiation of Th17 cells.The frequencies of Th17 cells in early AS rats were increased. ATRA could reduced the frequencies of Th17 cells and relieve AS process.