Abstract 10295: A Novel Pathway of miR30c-Regulated Platelet-derived PAI-1 in Type 2 Diabetic Mellitus
Background: Type II diabetes mellitus is associated with higher rates of thrombotic complications in patients with coronary artery disease. High level of PAI-1 has been found in type II diabetes, however, the mechanisms by which platelets mediate thrombotic pathways are less well understood.
Methods and Results: miR-30c was especially gradually down-expressed in leukocyte-depleted platelets (LDPs) from patients with pre-diabetic mellitus (pre-DM), non-complicated diabetic patients (NCDM) and diabetes mellitus type 2-coronary heart disease (DM-CHD). miR-30c level in DM-CHD was decreased 8-fold comparing to healthy individuals. Conversely, the expression of PAI-1 mRNA were up-expressed, and reached to peak in DM-CHD. Further analysis found that the total amount of PAI-1 protein in LDPs increased 4-fold~8-fold comparing to PPPs, and the amount of PAI-1 protein was high in NCDM and DM-CHD, but low in pre-DM and control. In luciferase reporter gene assay, miR-30c targets the 3’ untranslated region (3’ UTR) of PAI-1 mRNA through a miR-30c binding site. Transfection of miR-30c mimic into MEG-01, a megakaryoblastic cell line, significantly reduced PAI-1 protein level. Inhibition of miR-30c by transfecting miR-30c inhibitor significantly increased PAI-1 protein level. In vivo, there were significantly high levels of PAI-1 protein in LDPs and PPP from db/db mice compared with control mice, conversely, the expression of LDPs miR-30c in db/db mice was lower than those in control mice.
Conclusions: These results provide a novel pathway of miR30c- regulated platelet-derived PAI-1 in type 2 diabetic mellitus, indicating important implications regarding the regulation of fibrinolytic system by platelet miRNA under type 2 diabetic mellitus.
- © 2013 by American Heart Association, Inc.