Circulating miR-30c as a predictive biomarker of type 2 diabetes mellitus with coronary heart disease by regulating PAI-1/VN interactions.

AIMS

Type 2 diabetes mellitus (DM2) is associated with coronary heart disease (CHD) and is characterized by high levels of plasminogen activator inhibitor (PAI)-1. Circulating microRNAs have been reported as potential diagnostic biomarkers for DM2 and CHD. However, the underlying mechanisms have largely remained unclear.

MAIN METHODS

The changes of circulating miR-30c, PAI-1 and vitronetin (VN) in plasma from CHD, noncomplicated (NC) + DM2, CHD + DM2 subjects and control individuals were assessed by quantitative reverse transcription PCR (qRT-PCR) and ELISA assays, respectively. The effects of miR-30c on VN expression by targeting PAI-1 were assessed in vitro SMC and in ex vivo plasma, using bioinformatic analysis, miRNA transfection, luciferase assays, qRT-PCR and western blot, respectively.

KEY FINDINGS

We found that decreased circulating miR-30c was negatively correlated with the severity of coronary lesions and the resulting elevated PAI-1 and VN levels. Circulating miR-30c significantly distinguished between patients with CHD + DM2, NC + DM2, CHD and control subjects, and that were significantly associated with certain risk factors for progression from a normal individual to one with CHD + DM2. Furthermore, we also showed that miR-30c plays a previously unrecognized role in regulating the expression of VN levels via regulating PAI-1 levels in vitro SMC and in ex vivo plasma.

SIGNIFICANCE

These findings provide a novel regulatory mechanism of miR-30c in regulating PAI-1/VN interactions and that may serve as a diagnostic biomarker of DM2 that is complicated with CHD.