MicroRNA in atherothromobosis: is it useful as a disease marker?

Satoshi Fujii, Tomonori Sugiura, Yasuaki Dohi, Nobuyuki Ohte

Atherosclerosis is one of the major causes of death. Data from animal experiments suggest that atherosclerosis involves an inflammatory process of the vascular wall under hyperlipidemia. Atherothrombosis can become a serious complication of atherosclerosis leading to acute cardiovascular events such as myocardial infarction and stroke. Clinical applications to use this knowledge remain scarce. The plasma levels of vascular endothelium-enriched microRNA (miRNAs) in patients with atherosclerotic vascular disease could serve as a disease marker. In our laboratory vascular endothelium-enriched miRNA (miR-126) level was analyzed using quantitative RT polymerase chain reaction analysis (qRT-PCR) in plasma from patients with suspected coronary artery disease (CAD) according to the chest symptom or findings of electrocardiogram, or middle-aged male smokers. Endothelial function for peripheral small vessels was assessed using End-PAT 2000 and expressed as reactive hyperemia peripheral arterial tonometry (RH-PAT) index. In patients with suspected CAD miR-126 was not significantly changed in CAD patients. However, miR-126 was decreased in CAD patients who also have high levels of low-density lipoprotein (LDL) cholesterol. Interestingly, miR-126 was increased when LDL cholesterol was high in patients who did not have evident CAD on coronary angiography even though they have risk factors for CAD. In smokers serum cotinine levels were inversely correlated with endothelial function expressed as RH-PAT index and positively correlated with levels of metabolic parameters such as non-high-density lipoprotein (HDL) cholesterol and insulin resistance. More than half of the smokers could not completely attain smoking cessation and, thus, the RH-PAT index was not improved 8 weeks after the instruction of smoking cessation. However, changes in the RH-PAT index showed a significant correlation with those in systolic blood pressure. In smokers who completely attained smoking cessation, both RH-PAT index and plasma miR-126 values were increased. Thus, among patients with suspected CAD or subjects with coronary risk factors plasma levels of endothelium-enriched circulating miR-126 could be substantially altered. The results suggest a potential usefulness of miR-126 as a sensitive biomarker in assessing endothelial damage. Measurement of microRNA may serve as a useful tool for laboratory assays to determine high-risk patients for atherothromobotic vascular diseases.