title: Worse clinical outcomes in acute myocardial infarction patients with type 2 diabetes mellitus: relevance to impaired endothelial progenitor cells mobilization.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Cardiology, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ling
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.forename: Chunying
authors.initials: C
authors.lastname: Jiang
authors.forename: Chunmei
authors.initials: C
authors.lastname: Fang
authors.forename: Albert
authors.initials: A
authors.lastname: Ferro
authors.forename: Lina
authors.initials: L
authors.lastname: Kang
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000208:Acute Disease; D000368:Aged; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis* / Q000473:pathology* / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000097:blood; D051381:Rats; D015398:Signal Transduction; D013234:Stem Cells / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D020257:Ventricular Remodeling
chemical_list: D054377:Chemokine CXCL12; C101358:DAZL protein, human; D016601:RNA-Binding Proteins; D042461:Vascular Endothelial Growth Factor A