The Mechanism Study Of CD4 Positive T Cell And TGF-β1/MAPK Signal Pathway On Valvular Hyperblastosis And Fibrosis About Rheumatic Heart Disease

Objective Rheumatic heart disease is a kind of common and frequently-occurring disease in our country.In the early days,the patient suffered a Group A beta hemolytic streptococcus infection,leading to rheumatic fever.Then it make heart valve tissue hyperplasia and fibrosis,finally lead to dysfunction of heart valve through long-term development.In our country,rheumatic heart disease still has the high prevalence and is one of the major cardiovascular disease,which has serious harm to the health of young adults and brings huge economic burden for them,leading to chronic heart failure and death.It is accepted that Group A beta hemolytic streptococcus infection is the onset of action of rheumatic heart disease.However,it is not clear that how the heart valve lesion developing and what exact pathological change mechanism is.Therefor,fully understanding the exact pathogenesis mechanism of rheumatic heart disease and exploring the key targets would have the critical significance to prevent the disease,which will improve the health status of young adults and decrease the burden on social economy.Method Randomly selected 78 cases of patients of rheumatic heart disease with mitral stenosis and insufficiency in our hospital from January 2014 to June 2015,which are defined as RHD group including forty-one male cases and thirty-seven female cases and they are from thirty-five years old to sixty-two years old.Another group including thirty-eight male cases and thirty-five female cases with diseases of rupture of chordae tendinca or congenital heart disease are defined as CON group.They are from thirty-four years old to sixty-five years old.All patients were assessed valve form and thickening preoperative by cardiac ultrasonography and blood specimens were collected.The valve specimens were taken out and observated and recorded before test.The distribution of peripheral blood CD4 positive T cells were tested by flow cytometry and the serum concentration of TGF-β1was tested by ELISA in two groups.HE and Masson staining were down to detect fibrosis of heart valve.CD4 positive T cell infiltration and expression of TGF-β1,α-SMA,p38,JNK,ERK were detected in valves by immunohistochemistry.Real time polymerase chain reaction and western blotting were used to investigate the m RNA and protein expression of p38,JNK,ERK1/2,TGF-β1,collagen of type I,α-SMA.Result It is found that valves in RHD group are thickening and stenosis with varing degrees of calcification by UCG.All these lead limited opening and incomplete closing.While it could be seen that rupture of chordae tendinca in valve without thickening,associated with moderately or severe insufficiency in CON group.They were also verified have same looking intraoperative as by UCG.The mean distribution of peripheral blood CD4 positive T cells(46.1±4.7%)in RHD group was higher than that in CON group(P<0.05).What’s more,infiltrated CD4 positive T cells in valves of RHD group was also higher than that in CON group with significant difference(P<0.01).TGF-beta 1 concentration of peripheral serum in RHD group(the mean is31.326±2.087 ng/ml)is lower than that in CON group(the mean is 23.465±1.367 ng/ml)with a significant difference(P<0.05).However,the protein expression of TGF-beta 1in RHD group is higher that in CON group detected by immunohistochemistry and Western Blotting.The phosphorylation of JNK and p38 belonging to MAPK family in valve of RHD group,specially for phosphorylation of JNK,are higher than those in valves of CON group,with significant difference(P < 0.01).However,there is no statistical significant change of phosphorylation of ERK1/2.In addition,the synthesis of collagen of type I increases in RHD group than that in CON group with significant difference(P<0.01).It is also found that the expression of α-SMA in RHD group is higher than that in CON group,but there is no statistical significance between the two groups.Conclusion CD4 positive T cells participate in and maintain the process,which is from chronic rheumatic fever to rheumatic heart disease.CD4 positive T cells could secrete and express the cytokine of TGF-β1.TGF-β1 is coupled with the receptors on valvular interstitial cell surface,then activate mitogen activated protein kinase(MAPK)and transfer the signal to nuclear by TGF-β1/MAPK signal path,which could be increase collagen synthesis and valve interstitial cell hyperplasia and promote the development of valvular tissue fibrosis and lesion progression.Therefore,CD4 positive T cells and TGF-β1/MAPK signal path not only are involved in the process of valve lesion of rheumatic heart disease,but also are key part of the lesion progression.It will hopefully to uncovere the pathogenesis of valve disease,providing a new thought and target.