title: Elevated concentrations of Nɛ-homocysteinyl-lysine isopeptide in acute myocardial infarction: links with ADMA formation.
abstract: BACKGROUND
  A homocysteine (Hcy) metabolite, thioester Hcy-thiolactone, whose reaction with protein lysine residues affords N-homocysteinylated proteins, has been implicated in cardiovascular disease. Proteolytic turnover of N-homocysteinylated proteins generates the isopeptide Nɛ-homocysteinyl-lysine (N-Hcy-Lys).
  
  
  METHODS
  We determined N-Hcy-Lys in serum and a NO syntase inhibitor asymmetric dimethylarginine (ADMA), as well as symmetric dimethylarginine (SDMA) and glutathione in plasma by high performance liquid chromatography in 52 consecutive patients with acute myocardial infarction (AMI) recruited within the first 12 h following onset of chest pain. Associations of N-Hcy-Lys with markers of thrombin generation, oxidative stress, enhanced inflammation, fibrinolysis, and autoantibodies against homocysteinylated proteins were also analyzed.
  
  
  RESULTS
  N-Hcy-Lys concentrations, detectable in 45 (86.5%) patients (>0.1 μmol/L), were 127.3% higher compared with healthy controls. N-Hcy-Lys correlated with ADMA (r=0.50; p<0.001), SDMA (r=0.43; p<0.01), glutathione (r=0.37; p<0.05), fibrinogen (r=0.39; p<0.01) and plasminogen activator inhibitor-1 (r=0.32; p<0.05), but not with plasma total Hcy, anti-N-Hcy-protein autoantibodies, vitamin B(12), folate, interleukin-6, plasma thrombin-antithrombin (TAT) complexes, prothrombin fragments F1+2 or 8-isoprostaglandin F(2α) a marker of oxidative stress.
  
  
  CONCLUSIONS
  N-Hcy-Lys is increased in AMI patients and its formation is linked with the nitric oxide synthase inhibitor ADMA.
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Zaąbczyk
authors.forename: Rafał
authors.initials: R
authors.lastname: Głowacki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Machnik
authors.forename: Paweł
authors.initials: P
authors.lastname: Heród
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kazek
authors.forename: Hieronim
authors.initials: H
authors.lastname: Jakubowski
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D004151:Dipeptides / Q000097:blood*; D004727:Endothelium / Q000473:pathology; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress; D013917:Thrombin / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D004151:Dipeptides; C556024:N(epsilon)-homocysteinyl-lysine; C018524:N,N-dimethylarginine; D001120:Arginine; D013917:Thrombin