The Association And Mechanism Of Long Non-coding RNA And Environmental Factors In Coronary Heart Disease

Objective This study intends to explore the independent roles of long non-coding RNAs(lncRNAs)and their interaction with environmental factors in the pathogenesis of coronary heart disease(CHD);Further cellular experiments were used to reveal the role and mechanism of down-expression of lncRNA ENST00000609755.1 in HCAECs injury model which was induced by ox-LDL and provide theoretical basis for the development of epigenetic genetic markers and treatment of CHD.Method A hospital-based case-control study was conducted.A total of 590 CHD patients and 590 healthy volunteers without any evidence of cardiovascular diseases were assessed from December 2014 to December 2017 in the Fujian Medical University First Affiliated Hospital,Fujian Medical University Union Hospital and Fujian University of Traditional Chinese Medicine Affiliated People's Hospital,China.Questionnaire survey,health examination and molecular biology laboratory testing were conducted.LncRNAs microarray was used to screen the differentially expressed lncRNAs in the peripheral blood of the case and control populations and verified by qRT-PCR in large population samples;Multivariate logistic regression was used to explore the independent roles of long non-coding RNAs(lncRNAs)and their interaction with environmental factors in the pathogenesis of coronary heart disease(CHD).The oxidized low-density lipoprotein(ox-LDL)was used to treat human coronary artery endothelial cells to establish a model of coronary endothelial cell injury.After inhibiting the expression level of ENST00000609755.1 by siRNA,the mechanism of down-regulation of ENST00000609755.1 in the HCAECs injury model induced by ox-LDL were elucidated by observing the changes of organelle structure,cell viability,cell proliferation activity and apoptosis.Result(1)Multivariate logistic regression analysis showed that the risk factors for CHD were anxiety,overweight,and family history of CHD.And light diet,medium/ heavy-intensity and thinness were the protective factors.(2)The lncRNAs microarray showed that 320 lncRNAs were significantly different expressed between the two groups(FC> 2,P <0.05).Among them,ENST00000609755.1 was up-regulated in the case group,while ENST00000565648.1 and ENST00000450016.1 were down-regulated in the case group.(3)The population sample verification results showed that the expression level of ENST00000609755.1 in peripheral blood leukocytes of the case group was higher than that of the control group(P<0.05);The expression level of ENST00000565648.1 was lower than that of the control group(P<0.05);The expression level ofENST00000450016.1 showed no significant difference between the two groups(P>0.05).(4)The results of cell experiments showed that: after treated with 100 ?g/ml ox-LDL for 48 hours,the organelle structure of HCAECs changed,cell viability decreased,cell viability decreased and apoptosis increased,suggesting that ox-LDL-induced HCAECs injury model was successfully constructed.ENST00000609755.1 was highly expressed in the ox-LDL-induced HCAECs injury model(P<0.05);And down-regulated of ENST00000609755.1 weakened the damage effect of HCAECs induced by ox-LDL.Conclusion CHD is a complex disease co-regulation of environmental and genetic factors.lncRNAs are closely related to the occurrence and development of CHD.The changes in the expression levels of ENST00000609755.1 and ENST00000565648.1 may be involved in the occurrence and development of coronary heart disease.The high expression level of ENST00000609755.1 in HCAECs may be involved in the initiation of coronary heart disease by causing dysfunction of HCAECs.