Cyclophilin A Gene Polymorphism And Its Role Mediated Inflammatory Response In Coronary Heart Disease

Object To investigate the roles of gene polymorphism and pro-inflammatory activityof cyclophilin A in coronary atherosclerosis, and to explore the mechanisms ofcyclophilin A in inflammatory response.Methods DNA pool combined with quantitative PCR technique to observe thecorrelation between coronary artery disease and polymorphism of cyclophilin A,TNF-alpha, IL-6and IL-10. ELISA to detect the level of cyclophilin A, TNF-alpha,IL-6and IL-10level before and after percutaneous coronary intervention(PCI) incoronary artery disease(CHD) patients, and observed the correlation betweencyclophilin A level and inflammatory state in coronary artery disease.Immunohistochemical to detect the expression of cyclophilin A in coronaryatherosclerotic plaque and normal tissue. Western blot and coimmunoprecipitation toanalyze the effects of cyclophilin A knock-down on expression of ITK and T-bet in Tlymphocytes.Results Genotype and allele frequency of the SNP of M829in cyclophilin A gene hasa significant difference between200patients and200controls. Cyclophilin A829AAwas significantly higher than that of healthy controls. Genotype of797A/G and910A/G in IL-6gene was higher than that of healthy controls. There hasn't significantdifference between200patients and200controls in the allele frequency of the SNP ofTNF-α gene. The levels of cyclophilin A, IL-6and TNF-α were decreased after PCI inCHD, while IL-10levels gradually increased. Cyclophilin A was highly expressed incoronary atherosclerotic plaques. Expression and activity of ITK was declined whenknock-down of cyclophilin A, while T-bet was increased.Conclusion The polymorphism genotype of cyclophilin A829AA was significantlyhigher than that of healthy controls, may be related to CHD. There was a positivecorrelation between cyclophilin A level and inflammatory state in CHD, cyclophilin Amay be used as a indicator of postoperative inflammation and complications after PCI.Cyclophilin A prevented the differentiation of T cells to Th2subtype by Suppression of ITK activity, while promoting the differentiation to Th1subtype by inducingexpression of T-bet, which aggravated the inflammation in CHD.