Author + information
- Luigi M. Biasucci,
- Giulio La Rosa,
- Claudia Mandolini,
- Maria Chiara Grimaldi and
- Filippo Crea
Background: Type 2 diabetes mellitus (T2DM) is a major risk factors for myocardial infarction (MI), mostly because of an increased pro-inflammatory and pro-thrombotic milieu. Most of MI in T2DM are NSTEMI and often they have severe coronary artery disease at first presentation. We explored two novel mechanisms that may induce a pro-thrombotic status, in particular we assessed: 1) the down-regulation of the eNOS gene, as this gene has a biphasic activity: when eNOS expression is reduced eNOS gene loses its anti-aggregatory effect turning into pro-thrombotic. 2) an increased activity of Multidrug Resistence Protein 4 (MRP4) gene, that encodes for a transmembrane protein which drives drugs compounds out of the cell. In particular MRP4 has been associated to drugs resistance including aspirin.
Purpose: The aim of our study was to investigate whether eNOS and MRP4 genes are differently modulated in T2DM patients with NSTEMI vs patients with NSTEMI but not diabetes, as increased expression of these genes might explain a higher pro-thrombotic state.
Methods: MRP4 and eNOS mRNA expression were analyzed by RealTime PCR in platelets of 15 NSTEMI patients with (8) and without (7) T2DM compared to 20 patients with T2DM but without history of ischemic heart disease as control group. Normalization has been performed using beta2-microglobulin as housekeeping gene.
Results: Platelets MRP4 mRNA expression was significantly upregulated in NSTEMI patients without T2DM compared to control group (p< .05) and in NSTEMI T2DM patients compared to control group (p=0.014); no significant differences were found between NSTEMI with and without T2DM. Conversely platelets eNOS mRNA was significantly downregulated in NSTEMI with T2DM compared to NSTEMI without T2DM (p<.05) and controls (p< .001) and in NSTEMI without T2DM compared to control group (p< .001)
Conclusions: Our study shows a different modulation of MRP4 and of eNOS mRNA in NSTEMI patients. The significantly increased levels in MRP4 expression and decreased levels in eNOS expression in T2DM NSTEMI patients might explain the higher pro-thrombotic phenotype and cardiovascular risk of these patients and represent a significant risk factors for NSTEMI.
Poster Hall, Hall C
Saturday, March 18, 2017, 3:45 p.m.-4:30 p.m.
Session Title: Emerging Basic Science in Ischemic Heart Disease
Abstract Category: 1. Acute and Stable Ischemic Heart Disease: Basic
Presentation Number: 1251-301
- 2017 American College of Cardiology Foundation