Association Of Coronary Heart Disease With Mitochondrial Transcription Factor A

Coronary heart disease(CHD)has always been considered as the leading cause of death in the worldwide,and effective diagnostic methods have reduced its burden on global public health over the past few decades.However,in developing countries like China,the trend of suffering from CHD is still increasing.CHD is the pathological manifestation of coronary atherosclerosis.Mitochondrial dysfunction is resulted from the damage of mitochondrial DNA(mt DNA),which promotes the process of inflammation and apoptosis.Finally,these factors play a critical role in the development of atherosclerosis.Therefore,mt DNA damage may be associated with atherosclerosis.The mt DNA is packaged by mitochondrial transcription factor A(TFAM)and forms a mitochondrial nucleoid(mt DNA-protein complex)like histone,which preserves mt DNA integrity and stability and protects it from attack by oxidative stress.Meanwhile,TFAM can regulate the mt DNA copy number by promote mt DNA replication,thus protect mitochondrial function.Krish and his colleagues have described that overexpression of TFAM could prevent the reduction of mt DNA copy number in diabetic dorsal root ganglion(DRG)neurons and experimental diabetic neuropathy,thereby protecting DRG neurons from oxidative stress.Given the above,TFAM acts as one of the critical targets regulating mitochondrial biogenesis.Several studies have shown that mt DNA copy number of patients with coronary heart disease is significantly lower than the control group in peripheral blood.The change may reflect the increased cellular levels of oxidative stress and evaluate the severity of coronary heart disease.As compared to mt DNA,the variations of TFAM are characterized as regulating mitochondrion earlier and more direct.There were no reports about the association between CHD and TFAM.Therefore,the expression of TFAM m RNA in peripheral blood of CHD patients was tested to determine whether it was related to CHD.Objective: To investigate the relationship between peripheral blood TFAM content and CHD.Methods: A total of 144 patients who are suspected as CHD were enrolled in this literature.According to the results of coronary angiography(CAG),they were divided into CHD group(CAG showed at least one major vessel stenosis greater than 50%,101 subjects)and control group(CAG was negative,43 subjects),respectively.The data of participants,which included baseline characteristics,past illness history and blood index,were collected.The baseline characteristics covered sex,age,height,weight,blood pressure(SBP,DBP),tobacco,alcohol and BMI.The history of hypertension and diabetes mellitus consisted in past illness history.The blood index included TC,TG,HDL-C,LDL-C,FBG,BUN,Creatinin,UA,WBC,Neutrophil,Lymphocyte.Meahwhile,a quantitative real-time PCR-based method was used to measure expression of TFAM m RNA in peripheral blood.The expression was calculated by formula,2-ΔΔct.The Ct value represents the number of PCR cycles which the specimen expands to the specified threshold value.Through analysis the expression of TFAM m RNA,which was compared in CHD group and control group.Results: 1.CHD group,compared to control group,had higher of SBP[137.00(125.00,151.50)]vs[130.00(120.00,136.00)],male sex(64.4%)vs(41.9%),tobacco(50.5%)vs(27.9%),diabetes mellitus(28.7%)vs(7.0%),P<0.05.2.CHD group,compared to control group,had lower of TFAM m RNA content[0.75(0.57,1.01)]vs[0.91(0.67,1.57)],Lymphocyte(24.99±9.50)vs(30.38 ± 7.55).CHD group,compared to control group,had higher of WBC[6.69(5.69,8.44)]vs[5.88(5.33,7.02)],FBG[6.50(5.17,8.88)]vs[5.33(4.98,6.60)],Creatinin [66.50(55.53,78.18)]vs[61.20(54.10,71.60)],Neutrophil(66.4 1±11.69)vs(61.61±9.05),P <0.05.3.ROC curve analysis showed that area under the curve of TFAM m RNA content was used in the diagnosis of CHD was 0.646(P<0.01),the sensitivity and specificity were 81.4% and 32.7%,respectively.Conclusion: The expression of TFAM m RNA in CHD group is lower than the control group in peripheral blood.