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Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization

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-d...

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Autores principales: Ling, Lin, Shen, Yu, Wang, Kun, Jiang, Chunying, Fang, Chunmei, Ferro, Albert, Kang, Lina, Xu, Biao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511359/
https://www.ncbi.nlm.nih.gov/pubmed/23226370
http://dx.doi.org/10.1371/journal.pone.0050739
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author Ling, Lin
Shen, Yu
Wang, Kun
Jiang, Chunying
Fang, Chunmei
Ferro, Albert
Kang, Lina
Xu, Biao
author_facet Ling, Lin
Shen, Yu
Wang, Kun
Jiang, Chunying
Fang, Chunmei
Ferro, Albert
Kang, Lina
Xu, Biao
author_sort Ling, Lin
collection PubMed
description 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±56/10(6) mononuclear cells (MNCs) vs. 431±88/10(6) 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.
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spelling pubmed-35113592012-12-05 Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization Ling, Lin Shen, Yu Wang, Kun Jiang, Chunying Fang, Chunmei Ferro, Albert Kang, Lina Xu, Biao PLoS One Research Article 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±56/10(6) mononuclear cells (MNCs) vs. 431±88/10(6) 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. Public Library of Science 2012-11-30 /pmc/articles/PMC3511359/ /pubmed/23226370 http://dx.doi.org/10.1371/journal.pone.0050739 Text en © 2012 Ling et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ling, Lin
Shen, Yu
Wang, Kun
Jiang, Chunying
Fang, Chunmei
Ferro, Albert
Kang, Lina
Xu, Biao
Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization
title Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization
title_full Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization
title_fullStr Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization
title_full_unstemmed Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization
title_short Worse Clinical Outcomes in Acute Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Relevance to Impaired Endothelial Progenitor Cells Mobilization
title_sort worse clinical outcomes in acute myocardial infarction patients with type 2 diabetes mellitus: relevance to impaired endothelial progenitor cells mobilization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511359/
https://www.ncbi.nlm.nih.gov/pubmed/23226370
http://dx.doi.org/10.1371/journal.pone.0050739
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