Background and Objectives: The present study aimed to identify atherosclerosis-related circulating miRNAs and to evaluate their interaction with other cardiovascular risk markers to improve the prediction of atherosclerosis presence.
Methods: We used miRNA profiling to identify atherosclerosis-related miRNAs using serum of 8 non-atherosclerotic and 7 severe atherosclerotic ischemic stroke patients. Expression of the target miRNAs identified was validated in 38 non-atherosclerotic and 37 atherosclerotic patients. Associations of the target miRNAs with other cardiovascular risk markers to predict atherosclerosis presence were analyzed using forward logistic regression analysis. Interactions of miRNAs with risk markers in the prediction of atherosclerosis presence were analyzed using accuracy and discrimination analysis.
Results: miR-212, -30c, -372, -454, and, -744 were identified as atherosclerosis-related miRNAs. Only miR-212 showed a significant increase in expression in atherosclerotic patients of the validation population. Of various established markers tested, hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a) were independently related with atherosclerosis presence in the validation population. miR-212 significantly increased the accuracy (three markers, 78.55%; three markers+miR-212, 84.6%) and area under the receiver operating characteristic curve (three markers, 0.8258; three markers+miR-212, 0.8646) of atherosclerosis prediction by the three existing markers.
Conclusion: We identified circulating miR-212 as a novel marker of atherosclerosis. miR-212 synergistically enhanced the prediction of atherosclerosis-presence in combination with hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a). Thus, miR-212 is expected to improve the prediction of atherosclerosis using peripheral blood of patients.