4111Clinical Implications of microRNA score in discriminating vasospatic angina from atherothrombotic angina or non-coronary chest pain

Abstract

Vasospastic angina (VA) is difficult to diagnose with history alone and provocative procedure has limitation due to invasiveness. Herein, we investigated the diagnostic implication of circulating microRNA (miR) profile in discriminating VA patients from atherothrombotic angina (AA) with obstructive coronary lesion as well as no/insignificant coronary artery lesion (NCL). Patients who underwent coronary angiography (CAG) for chest pain were screened. Blood samples were obtained during CAG and serum miR-17, miR-92a, miR-126, miR-145, miR-221, and miR-222 expression was assessed. We also evaluated pathophysiologic role of miRs in regulating endothelial NO synthase (eNOS) expression usinghuman coronary artery endothelial cells (hCAECs). hCAECs were cultured and transfected with miR mimics and miR inhibitors to evaluate the eNOS expression by western blots and qRT-PCR. Among 121 patients, 46 patients were diagnosed as VA, 49 as AA, and 26 as NCL. Concentration of miR profiles were independent to conventional cardiovascular risk factors and their expression levels were significantly different across VA, AA, and NCL group. A score, based on the levels of six miRs was able to efficiently discriminate VA patients from AA or NCL patients. In hCAECs, miR-17 mimic, miR-92a mimic, and miR-126 mimic transfection suppress eNOS expression. We also found that inhibitors of miR-17 and miR-92a could reverse the inhibition of eNOS induced by lipopolysaccharide treatment in hCAECs. In conclusion, this data demonstrated that profiling circulating miRs can identify VA patients among patients presenting angina. It also advances our understanding about pathologic contribution of miRs in vasospasm by regulating eNOS expression.