MiR-486 and miR-92a Identified in Circulating HDL Discriminate between Stable and Vulnerable Coronary Artery Disease Patients

Abstract

Small non-coding microRNAs (miRNAs) are implicated in gene regulation, including those involved in coronary artery disease (CAD). Our aim was to identify whether specific serum miRNAs present in the circulating lipoproteins (Lp) are associated with stable or vulnerable CAD patients. A cardiovascular disease-focused screening array was used to assess miRNAs distribution in sera collected from 95 CAD patients: 30 with stable angina (SA), 39 with unstable angina (UA), 26 at one month after myocardial infarction (MI) and 16 healthy control subjects. We found that miR-486, miR-92a and miR-122 presented the highest expression in CAD sera. These miRNA together with miR-125a, miR-146a and miR-33a were further individually analyzed by TaqMan assays. The results were consistent with PCR-array screening data that all of these miRNAs were significantly increased in CAD patients compared to controls. Using a binary logistic regression model, we established that miR-486 and miR-92a in association with some high-density lipoprotein (HDL) components can designate vulnerable CAD patients. Further, all classes of Lp were isolated from sera by density gradient ultracentrifugation. Analysis of the selected miRNAs in each Lp class showed that they were associated mainly with HDL, miR-486 and miR-92a having the highest levels. In UA and MI patients, miR-486 prevailed in HDL2, while miR-92a prevailed in HDL3, and their levels discriminate between stable and vulnerable CAD patients. We identified two circulating miRNAs that in association with some lipid metabolism biomarkers can be used as an additional tool to designate vulnerable CAD patients.

microRNAs in lipoprotein and lipid metabolism: from biological function to clinical application

“…From the nine miRNAs quantified by Wagner's group, miR-223-3p was also reported as the most concentrated in LDLs from healthy subjects [7]. Moreover, miR-92a-3p has been repeatedly identified as one of the most abundant miRNA carried by LDLs and IDLs [6][7][8].…”

“…Most importantly, the authors concluded that these differences in HDL-carried miR-486-5p and miR-92a-3p concentrations may discriminate between stable and vulnerable CAD patients [8]. Interestingly, miR-92a-3p has been identified as one of the most concentrated miRNAs in HDLs by Wagner et al [7].…”

“…Very recently, Niculescu et al showed that miR-486-5p and miR-92a-3p were upregulated in the serum of patients with CAD [including stable angina (SA), unstable angina (UA) and myocardial infarction (MI)] compared to healthy subjects ( Table 2), and that these differences were also found significant in the HDL 2 and HDL 3 subpopulations [8]. Most importantly, the authors concluded that these differences in HDL-carried miR-486-5p and miR-92a-3p concentrations may discriminate between stable and vulnerable CAD patients [8].…”

“…As for HDLs, IDL and LDL particles were also found to transport miRNAs in circulation [6][7][8]. Despite the recognized implication of LDLs in atherosclerosis development and the strong association between high LDL-C levels and increased risk of CVDs [4], the LDLs' miRNA cargo has been less studied than that of HDLs.…”

“…However, the role of lipoprotein-bounded miRNAs as endocrine regulators has recently emerged. Although studies on lipoprotein-transported miRNAs suggest distinct miRNA profiles in the two major lipoproteins found in circulation, the data support that miRNAs have a stronger role in high-density lipoprotein (HDL) than in low-density lipoprotein (LDL) in regulating their metabolic functions [6][7][8]. The discovery of miRNAs transported by lipoproteins thus opens up the way for two main clinical applications: biomarkers of diseases and targeted therapies.…”