title: Elevated level of pro-inflammatory eicosanoids and EPC dysfunction in diabetic patients with cardiac ischemia.
abstract: BACKGROUND
  Circulating endothelial progenitor cells (EPCs) are recruited from the blood system to sites of ischemia and endothelial damage, where they contribute to the repair and development of blood vessels. Since numerous eicosanoids including leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) have been shown to exert potent pro-inflammatory activities, we examined their levels in chronic diabetic patients with severe cardiac ischemia in conjunction with the level and function of EPCs.
  
  
  RESULTS
  Lipidomic analysis revealed a diabetes-specific increase (p<0.05) in inflammatory and angiogenic eicosanoids including the 5-lipoxygenase-derived LTB (4.11±1.17 vs. 0.96±0.27 ng/ml), the lipoxygenase/CYP-derived 12-HETE (117.08±35.05 vs. 24.34±10.03 ng/ml), 12-HETrE (17.56±4.43 vs. 4.15±2.07 ng/ml), and the CYP-derived 20-HETE (0.32±0.04 vs. 0.06±0.05 ng/ml) the level of which correlated with BMI (p=0.0027). In contrast, levels of the CYP-derived EETs were not significantly (p=0.36) different between these two groups. EPC levels and their colony-forming units were lower (p<0.05) with a reduced viability in diabetic patients compared with non-diabetics. EPC function (colony-forming units (CFUs) and MTT assay) also negatively correlated with the circulating levels of HgA1C.
  
  
  CONCLUSIONS
  This study demonstrates a close association between elevated levels of highly pro-inflammatory eicosonoids, diabetes and EPC dysfunction in patients with cardiac ischemia, indicating that chronic inflammation impact negatively on EPC function and angiogenic capacity in diabetes.
authors.affiliation: Cardiac Research Laboratory at the Felsenstein Medical Research Institute, Rabin Medical Center, Petah-Tikva and the Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Issan
authors.forename: Edith
authors.initials: E
authors.lastname: Hochhauser
authors.forename: Austin
authors.initials: A
authors.lastname: Guo
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Gotlinger
authors.forename: Ran
authors.initials: R
authors.lastname: Kornowski
authors.forename: Dorit
authors.initials: D
authors.lastname: Leshem-Lev
authors.forename: Eli
authors.initials: E
authors.lastname: Lev
authors.forename: Eyal
authors.initials: E
authors.lastname: Porat
authors.forename: Eitan
authors.initials: E
authors.lastname: Snir
authors.forename: Carl I
authors.initials: CI
authors.lastname: Thompson
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
authors.forename: Michal
authors.initials: M
authors.lastname: Laniado-Schwartzman
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000097:blood; D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015992:Body Mass Index; D002470:Cell Survival; D002853:Chromatography, Liquid; D003920:Diabetes Mellitus / Q000097:blood* / Q000503:physiopathology; D015777:Eicosanoids / Q000097:blood*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D007975:Leukotriene B4 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000503:physiopathology; D010455:Peptides / Q000097:blood; D013234:Stem Cells / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D015777:Eicosanoids; D006023:Glycoproteins; D006893:Hydroxyeicosatetraenoic Acids; D008055:Lipids; D010455:Peptides; D007975:Leukotriene B4; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D040301:Vascular Endothelial Growth Factor Receptor-2