PMID- 23226370
OWN - NLM
STAT- MEDLINE
DCOM- 20130523
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 11
DP  - 2012
TI  - Worse clinical outcomes in acute myocardial infarction patients with type 2 
      diabetes mellitus: relevance to impaired endothelial progenitor cells 
      mobilization.
PG  - e50739
LID - 10.1371/journal.pone.0050739 [doi]
LID - e50739
AB  - 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-1alpha 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.
FAU - Ling, Lin
AU  - Ling L
AD  - Department of Cardiology, The Affiliated Drum Tower Hospital, School of Medicine, 
      Nanjing University, Nanjing, China.
FAU - Shen, Yu
AU  - Shen Y
FAU - Wang, Kun
AU  - Wang K
FAU - Jiang, Chunying
AU  - Jiang C
FAU - Fang, Chunmei
AU  - Fang C
FAU - Ferro, Albert
AU  - Ferro A
FAU - Kang, Lina
AU  - Kang L
FAU - Xu, Biao
AU  - Xu B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121130
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokine CXCL12)
RN  - 0 (DAZL protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Acute Disease
MH  - Aged
MH  - Animals
MH  - Bone Marrow Cells/pathology
MH  - *Cell Movement
MH  - Chemokine CXCL12/blood
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Endothelial Cells/*pathology
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Myocardial Infarction/complications/*diagnosis/*pathology/physiopathology
MH  - Neovascularization, Physiologic
MH  - Prognosis
MH  - RNA-Binding Proteins/blood
MH  - Rats
MH  - Signal Transduction
MH  - Stem Cells/*pathology
MH  - Vascular Endothelial Growth Factor A/blood
MH  - Ventricular Dysfunction, Left/blood/complications/pathology/physiopathology
MH  - Ventricular Remodeling
PMC - PMC3511359
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/12/12 06:00
MHDA- 2013/05/25 06:00
PMCR- 2012/11/30
CRDT- 2012/12/11 06:00
PHST- 2012/09/01 00:00 [received]
PHST- 2012/10/24 00:00 [accepted]
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/05/25 06:00 [medline]
PHST- 2012/11/30 00:00 [pmc-release]
AID - PONE-D-12-26692 [pii]
AID - 10.1371/journal.pone.0050739 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(11):e50739. doi: 10.1371/journal.pone.0050739. Epub 2012 Nov 30.