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Worse clinical outcomes in acute myocardial infarction patients with type 2 diabetes mellitus: relevance to impaired endothelial progenitor cells mobilization.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (11), pp. e50739. Date of Electronic Publication: 2012 Nov 30. - Publication Year :
- 2012
-
Abstract
- Background: Although the clinical outcome of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (T2DM) is well established to be worse than for non-diabetic patients, the reasons for this remain unclear. We hypothesized that this may be related to impairment of bone marrow-derived endothelial progenitor cells (EPCs) mobilization.<br />Methodology/principal Findings: We observed short term bone marrow EPCs mobilization and long term clinical outcomes in 62 AMI patients with or without T2DM and investigated EPCs levels as well as bone marrow pathway changes in a rat model of diabetes after AMI. Patients with T2DM exhibited a delay (peak time diabetics vs. non-diabetics: day 7 vs. day 5) and a decrease in EPCs mobilization (diabetics vs. non-diabetics: 285±56/10⁶ mononuclear cells (MNCs) vs. 431±88/10⁶ MNCs, p<0.05) within one month after AMI. Plasma levels of VEGF and SDF-1α as well as of hsCRP were higher in T2DM patients. Over a mean of 2.26 years follow-up, T2DM patients exhibited a pronounced decrease in LVEF as well as an increase in clinical events. Glucose (HR 2.01, 95% CI 1.42-2.85, p = 0.008), first day EPC (HR 0.974, 95% CI 0.952-0.997, p = 0.02) and seven day EPCs (HR 0.966, 95% CI 0.945-0.988, p = 0.003) were independent prognostic variables for cardiovascular mortality. In a diabetic rat model of AMI, decreased circulating EPCs was accompanied by lower expression of phospho-Akt, phospho-eNOS, HIF, MMP-9 and MMP-9 activity in the bone marrow as well as impaired cardiac function, angiogenesis and increased left ventricle remodeling.<br />Conclusions/significance: Bone marrow EPCs mobilization is delayed and reduced in diabetes, with impaired HIF/p-Akt/p-eNOS/MMP-9 signaling. This is likely to contribute to the deterioration in cardiac function and worsened clinical outcome seen in patients with T2DM.
- Subjects :
- Acute Disease
Aged
Animals
Bone Marrow Cells pathology
Chemokine CXCL12 blood
Female
Follow-Up Studies
Humans
Male
Myocardial Infarction complications
Myocardial Infarction physiopathology
Neovascularization, Physiologic
Prognosis
RNA-Binding Proteins blood
Rats
Signal Transduction
Vascular Endothelial Growth Factor A blood
Ventricular Dysfunction, Left blood
Ventricular Dysfunction, Left complications
Ventricular Dysfunction, Left pathology
Ventricular Dysfunction, Left physiopathology
Ventricular Remodeling
Cell Movement
Diabetes Mellitus, Type 2 complications
Endothelial Cells pathology
Myocardial Infarction diagnosis
Myocardial Infarction pathology
Stem Cells pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23226370
- Full Text :
- https://doi.org/10.1371/journal.pone.0050739