title: Nitric oxide from mononuclear cells may be involved in platelet responsiveness to aspirin.
abstract: BACKGROUND
  Several mechanisms have been proposed to explain why some platelets have a reduced response to aspirin (ASA). Among them, it was reported an increased circulating level of vitamin-D-binding protein (DBP). In addition, nitric oxide (NO) released from mononuclear cells was involved in the antiplatelet effects of ASA. The aim was to analyse the relationship between platelet response to ASA and both NO generation and vitamin-D-binding protein content in mononuclear cells.
  
  
  METHODS
  Mononuclear cells were obtained from patients with stable coronary artery disease that were divided by a platelet functionality test (PFA-100) as ASA-sensitive (n=23) and ASA resistant (n=27).
  
  
  RESULTS
  Both the release of NO (determined by nitrite+nitrate concentration) and the expression of endothelial-type NO synthase (eNOS) were higher in mononuclear cells from ASA sensitive as compared with those from ASA-resistant patients. There was a positive correlation between either the release of NO and the expression of eNOS protein in mononuclear cells with the ability of ASA to inhibit platelet activity. DBP content in mononuclear cells was higher in ASA resistant than in ASA sensitive. The level of DBP content in mononuclear cells was negatively associated with the ability of ASA to inhibit platelets. However, in vitro experiments suggested that there was no association between DBP and NO production by mononuclear cells.
  
  
  CONCLUSIONS
  Mononuclear cells from patients with platelets with lower responsiveness to ASA showed a reduced ability to produce NO.
authors.affiliation: Cardiovascular Research Unit, Cardiology Department of Hospital Clínico San Carlos de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Medicine School, Complutense University, Madrid, Spain.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: López-Farré
authors.forename: Javier
authors.initials: J
authors.lastname: Modrego
authors.forename: Luis
authors.initials: L
authors.lastname: Azcona
authors.forename: Reddy
authors.initials: R
authors.lastname: Guerra
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura
authors.forename: Pablo
authors.initials: P
authors.lastname: Rodríguez
authors.forename: José J
authors.initials: JJ
authors.lastname: Zamorano-León
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
mesh_terms: D000368:Aged; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014809:Vitamin D-Binding Protein / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D014809:Vitamin D-Binding Protein; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D001241:Aspirin
keywords: Aspirin; mononuclear cells; nitric oxide; platelets; vitamin-D-binding protein