A Study On The Relationship Between The Expression Of SREBPs And Intron Shear Forming MiR-33 Circulation And Risk Factors Of Coronary Heart Disease

Objective: Coronary artery disease(CAD)is the leading cause of death worldwide and characterized by the formation of atherosclerotic plaques in the arterial wall.Abnormal lipid metabolism plays an important role in the development and progression of CAD.Early prevention and early diagnosis are the key to prevent the occurrence of cardiovascular and cerebrovascular events which lead by the CAD pathogenesis.A large number of studies have reported that Sterol regulatory element-binding proteins(SREBPs)are the major transcription factors that regulate lipid homeostasis,and alteration of its’ expression may be very crucial to the lipid metabolism homeostasis.The aim of this study was to investigate the changes of the relative expression levels of SREBPs(SREBP1,SREBP2)in peripheral blood leukocytes and plasma miR-33 which is co-transcribed with SREBP in CAD patients and make an evaluation on whether it could be a potential CAD diagnostic biomarker.Methods: Total peripheral blood RNA was isolated from 170 CAD patients and120 healthy people in Taihe Hospital.SREBP1 and SREBP2 mRNA expression level were detected by Real-time quantitative PCR(qPCR),40 CAD patients and 40 healthy people plasma miR-33 expression level were also detected by Real-time quantitative PCR(qPCR).The sensitivity and specificity of SREBPs and miR-33 for diagnosis of CAD were evaluated by receiver operating characteristic(ROC)curve and area under the curve(AUC).Results: SREBPs expression comparison between healthy control and case were made using non-parameter test.SREBP1 relative expression level in controls were0.03764±0.03538,which is significant higher than the corresponding figure in CAD group(0.01520±0.01237,P<0.01);SREBP2 expression level in control group(0.07912±0.06966)were also significant higher than CAD group(0.05226±0.05086,P<0.01);The area under the ROC curve of SREBP1 was 0.734(0.677-0.790),sensitivity and specificity were 46.2% and 87.3%,respectively.The area under the ROC curve of SREBP2 was 0.697(0.602-0.791),sensitivity and specificity were67.7% and 72.7%,respectively.The area under the ROC curve of miR-33 a was 0.814(0.731~0.898).The area under the ROC curve of miR-33 b was 0.951(0.911~0.991).Conclusion: Circulating expression levels of SREBPs and miR-33 were decreased in CAD patients and could be a potential biomarker for diagnosis of CAD.