Aberrant expression of plasma microRNA-33a in an atherosclerosis-risk group

In order to investigate whether plasma microRNA-33a (miR-33a) can be a biomarker for the early detection of atherosclerosis and to reexamine the assumption that miR-33a represses the expression of ABCA1, we compared the expression levels of miR-33a and ATP-binding cassette A1 (ABCA1) using human plasma and supernatants of macrophage cultured media. We first separated ample number of plasma samples from left-over whole blood samples based on the criteria for normal or dyslipidemia, and stored them at -20 °C until use. Then we selected 18 plasma samples for each normal, athero-risk and treated group using a metabolic disease cohort in which candidate subjects have participated. For classifying into three groups, we primarily relied on the records of physicians' comments, prescriptions, treatment history, lipid profiles and test results from medical equipment aimed at the diagnosis for atherosclerosis or cardiovascular disease. After collecting the final 54 plasma samples, we analyzed and compared the expression levels of miR-33a and ABCA1 at the plasma levels. In the comparison of plasma levels of the three groups, the miR-33a expression level of athero-risk group was 5.01-fold higher than that of normal group. Meanwhile, in the culture of foam cells transfected with anti-miR-33a oligonucleotides, the miR-33a level significantly decreased, while ABCA1 level significantly increased. The results suggest that enhanced expression of miR-33a might induce cholesterol accumulation and aggravate inflammation in vessel walls by suppressing the expression of ABCA1 in macrophages. Thus, plasma miR-33a can be considered as a candidate biomarker of atherosclerosis.