Role Of Immunoglobulins And Co-stimulatory Molecules In Pathogenesis Of Coronary Heart Disease

Objective To investigate functions of immunoglobulins,CD40/CD40ligand system and CD134/CD134ligand system on immunologic mechanism of coronary heart disease(CHD).Methods42healthy male adult rabbits were divided into6groups randomly. Normal control group(N):fed with normal food.Normal control and CSA group(N+CSA):fed with normal food and given CSA10mg/kg/d for4weeks.CHD group(CHD):fed with1.5%cholesterol diet and intervened with iliac artery balloon injury at the end of fourth week.CHD and CSA group(CHD+CSA):fed with1.5%cholesterol diet, intervened with iliac artery balloon injury at the end of fourth week and given CSA10mg/kg/d for4weeks. Restenosis group(RS):fed with1.5%cholesterol diet, intervened with iliac artery balloon injury at the ends of fourth and eighth week. Restenosis and CSA group(RS+CSA):fed with1.5%cholesterol diet, intervened with iliac artery balloon injury at the ends of fourth and eighth week and given CSA10mg/kg/d for4weeks. All rabbits were killed at the end of twelfth week. All rabbits were weighted at the beginning and ending of the study. Peripheral venous blood were taken both at the beginning and ending of the study to measure routine blood tests, liver and kidney function, blood lipids, and immunoglobulins including IgE,IgM, IgG. Iliac arteries were taken once rabbits were killed. Part of the iliac arteries were conserved at the temperature of-80℃,which were then used to measure mRNA expressions of CD40, CD40ligand(CD40L), CD134and CD134ligand (CD134L) through reverse transcription and real-time fluorescent quantitative polymerase chain reaction techniques. Another part were preserved in formaldehyde, then used for histological observation (including neointimal proliferation and vascular remodeling through hematoxylin and eosin staining, and the ratio of positive CD40,CD40L,CD134and CD134L cells through immunohistochemical methods).Data were analyzed through SPSS software(version18.0), P<0.05is of statistically significant difference.Results Unfortunately1rabbit of RS group died from bleeding caused by iliac artery balloon injury at the ending of eighth week, so41rabbits were finally enrolled in the study. There were no significant differences among the basal data.(1)Only changes of high density lipoprotein cholesterol(HDLc) and low density lipoprotein cholesterol (LDLc) in blood indexes were of statistical significance among the6groups.The HDLc and LDLc increases became greater from N group, CHD group and up to RS group(P<0.05).The HDLc increases of the groups with CSA intervention were lower than those without CSA intervention respectively(P<0.05), while the LDLc increases of the groups with CSA intervention were higher than those without CSA intervention(P<0.05).(2)There were no significant differences of IgE, IgM, IgG changes among all groups, and no correlations between immunoglobulins and neointimal proliferation, vascular remodeling.(3) Rising trends of CD40, CD40L, CD134, CD134L mRNA expressions were found from N group, CHD group to RS group(P>0.05).The ratio of positive CD40,CD40L,CD134and CD134L cells in CHD and RS group was higher than that in N group(P<0.05). Positive correlation were found among CD40,CD40L,CD134and CD134L mRNA expressions(P<0.01),between their mRNA expressions and IT,IA,IEL,EEL(P<0.05),and between the ratio of positive CD40, CD40L, CD134,CD134L cells and IHI(P<0.05).While negative correlation were found between the ratio of positive CD40,CD40L,CD134and CD134L cells and LA(P<0.05).(4)Between the groups with CSA intervention and those without CSA intervention respectively, no statistical differences of changes in IgE,IgM,IgG, and of CD40,CD40L,CD134,CD134L mRNA expressions and of the positive-cell ratio, and of indexes belongs to neointimal proliferation,vascular remodeling were found.Conclusion (1)There were no changing of serum IgE,IgM,IgG in CHD and RS rabbits compared with normal ones.(2) CD40/CD40L and CD134/CD134L maybe participate in neointimal proliferation,vascular remodeling through mediating inflammatory immune response.(3)On one hand CSA may have anti-atherosclerosis function through its immunosuppressive characteristics, on the other hand CSA may contribute to the pathobiology of atherosclerosis through neointimal proliferation and blood lipid profiles changing. The mechanism of CSA on CHD needs to be studied intensively.