title: Assay of oxidized fibrinogen reactivity (OFR) as a biomarker of oxidative stress in human plasma: the role of lysine analogs.
abstract: BACKGROUND
  There is accumulating evidence that fibrinogen is also a biomarker of oxidative stress in human plasma. Results of in vitro studies demonstrated that fibrinogen can bind to apolipoprotein(a) [apo(a)] component of lipoprotein(a) [Lp(a)] through both lysine-sensitive and lysine-insensitive mechanisms. The goal of the present study was to investigate oxidized fibrinogen reactivity (OFR) as a biomarker of oxidative stress in human plasma in the presence and absence of lysine analogs.
  
  
  METHODS
  Citrate anticoagulated peripheral venous blood samples were collected from 65 (36 M/29 F) consecutive patients with various peripheral vascular diseases. After centrifugation, the plasma was used promptly. Plasma OFR was determined in duplicate using a recently described kinetic photometric assay (358 nm, 37 degrees C) in the presence and in the absence of lysine analogs.
  
  
  RESULTS
  The inclusion of tranexemic acid (TRA) or epsilon-aminocaproic acid in the incubation medium resulted in a rapid increase in OFR in a dose-dependent manner. The peak effect was observed at a final concentration of 200 mmol/L TRA. OFR was significantly higher in patient plasma assayed in the presence of TRA compared with no TRA (163.1 +/- 73.5 vs. 63.4 +/- 20.7 U/L; p < 0.0001). Bound OFR was also significantly higher than free OFR (99.7 +/- 56.3 vs. 63.4 +/- 20.7; p < 0.001).
  
  
  CONCLUSIONS
  On the basis of the present results it appears that oxidized fibrinogen resides in plasma in two compartments: free and bound to apo(a) of Lp(a). The relatively simple and cost-effective kinetic approach applied in this study makes routine determination of OFR available as a biomarker of oxidative stress, separately in both compartments.
authors.affiliation: Department of Vascular Surgery, Faculty of Medicine, Semmelweis University, Budapest, Hungary. laszlo.selmeci@googlemail.com
authors.forename: László
authors.initials: L
authors.lastname: Selmeci
authors.forename: Leila
authors.initials: L
authors.lastname: Seres
authors.forename: Mária
authors.initials: M
authors.lastname: Székely
authors.forename: Pál
authors.initials: P
authors.lastname: Soós
authors.forename: György
authors.initials: G
authors.lastname: Acsády
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000614:Aminocaproates / Q000737:chemistry; D053241:Apoprotein(a) / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D005260:Female; D005340:Fibrinogen / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D016491:Peripheral Vascular Diseases / Q000097:blood; D014148:Tranexamic Acid / Q000737:chemistry
chemical_list: D000614:Aminocaproates; D015415:Biomarkers; D014148:Tranexamic Acid; D005340:Fibrinogen; D053241:Apoprotein(a); D008239:Lysine