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© 2012 Ling et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

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.

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.

Details

Title
Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization
Author
Lin, Ling; Shen, Yu; Wang, Kun; Jiang, Chunying; Fang, Chunmei; Ferro, Albert; Kang, Lina; Xu, Biao
First page
e50739
Section
Research Article
Publication year
2012
Publication date
Nov 2012
Publisher
Public Library of Science
e-ISSN
19326203
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1351068014
Copyright
© 2012 Ling et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.