| Background and objective:The chest pain and associated symptoms result from a lack of blood flow and oxygen delivery to the myocardium due to blockage in the coronary arteries. Atherosclerosis is a chronic, progressive, inflammatory disease with a long asymptomatic phase. Therefore, discovering atherosclerosis, changing one’s lifestyle and treating the disease at an early stage are very important. Finding sensitive and uninvasive biomarkers of atherosclerosis in blood is of practical significance. MicroRNAs (miRNAs) are small, noncoding regulatory RNAs. They inversely regulate the expression of their target genes at the posttranscriptional level by inhibiting translation or causing the degradation of the target messenger RNA (mRNA). MiRNAs play a crucial role in the development of animals, regulating the formation of tissues and organs. Previous studies have demonstrated that miRNAs are present in clinical samples of plasma and serum in a remarkably stable form, and they are often regulated in a tissue- and pathology-specific manner. The use of circulating miRNAs as clinical biomarkers has generated great interest. Up to now, more and more circulating miRNAs have been reported as novel biomarkers in multiple cardiovascular diseases for diagnosis of the disease, risk stratification and prognosis judgement. We want to find new biomarkers of subclinical coronary atherosclerosis by analyzing serum biochemical biomarkers and novel microRNAs from serum microRNA profiles.Material and Methods:Subjects who underwent CTA for the assessment of coronary artery disease (CAD) were studied. Clinical data and blood samples of the subjects were collected. Biochemical biomarkers including homocysteine (Hcy) were measured and solexa sequencing followed by bio informatics analysis was used to predict novel miRNAs. QRT-PCR was used for novel miRNAs validation.Results:1 Age, smoking, high blood pressure, serum TG and LDL-C were closely related to the severity of coronary disease. Age, smoking and LDL-C independently predicted the presence of calcified plaque.2 Hey was an independently risk factor of the severity of coronary disease and Hey was also found an independent predictor for the presence of calcified plaque. The OR of Hcy (>15μmol/L) for>50% stenosis was 2.212 (95% CI=1.119 to 4.375, p=0.022) and the OR for Hey (>15μmol/L) for calcification was 1.668 (95% CI=1.030 to 2.699, p=0.037) respectively.3 Solexa sequencing followed by bioinformatics analysis was used to predict novel miRNAs in control individuals (n=15), coronary disease (AS) patients (n=15) and unstable angina pectoris (UAP) patients (n=15). Three miRNAs were discovered and validated in 80 control individuals,80 AS patients and 80 UAP patients by quantitative reverse transcriptase polymerase chain reaction.4 N1, N2 and N3 were all expressed in the three groups. N1 and N3 were expressed at the highest levels in the AS group.5 We used target gene prediction tools and GO analysis to analyze the main functions of N1 and N3 discovered in our study. The results showed that N1 and N3 had more than one function that may be involved in the disease, including the regulation of Rho protein signal transduction, cell migration, and the induction of apoptosis.Conclusion:Our study further verified the relationship between traditional risk factors and coronary atherosclerosis disease. Hcy was proved an independent risk factor of the severity of coronary disease and the presence of calcified plaque. Our study established the miRNA profiles of coronary atherosclerosis disease and UAP disease. Novel miRNAs (N1, N2 and N3) were discovered and identified. Among the three novel miRNAs, N1 and N3 were significantly higher in group of coronary atherosclerotic plaque and may be new potential biomarkers for coronary atherosclerosis. |
