title: Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in male cigarette smokers.
abstract: OBJECTIVE
  The effects of ω-3 fatty acids on endothelial function, fibrinolysis and platelet function are uncertain. We investigated the effects of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis, and platelet and monocyte activation in healthy cigarette smokers; a group at increased risk of myocardial infarction.
  
  
  METHODS
  Twenty cigarette smokers were recruited into a randomised, double-blind, placebo-controlled, crossover trial of ω-3 fatty acid supplementation.
  
  
  METHODS
  ω-3 fatty acid supplements (2 g/day) or placebo for a 6-week period.
  
  
  METHODS
  Peripheral blood was taken for analysis of platelet and monocyte activation, and forearm blood flow (FBF) was assessed in a subset of 12 smokers during intrabrachial infusions of acetylcholine, substance P and sodium nitroprusside. Stimulated plasma tissue plasminogen activator (t-PA) concentrations were measured during substance P infusion.
  
  
  RESULTS
  All vasodilators caused dose-dependent increases in FBF (p<0.0001). Compared with placebo, ω-3 fatty acid supplementation led to greater endothelium-dependent vasodilatation with acetylcholine and substance P (p=0.0032 and p=0.056). Substance P caused a dose-dependent increase in plasma t-PA concentrations (p<0.0001) that was greater after ω-3 fatty acid supplementation compared with placebo (8.8±2.3 IU ml(-1) vs 3.6±1.1 IU ml(-1); p=0.029). ω-3 fatty acids did not affect platelet-monocyte aggregation, platelet P-selectin or CD40L, or monocyte CD40.
  
  
  CONCLUSIONS
  We have demonstrated for the first time that ω-3 fatty acids augment acute endothelial t-PA release and improve endothelial vasomotor function in cigarette smokers. Improved endogenous fibrinolysis and endothelial function may represent important mechanisms through which ω-3 fatty acids confer potential cardiovascular benefits.
authors.affiliation: Centre for Cardiovascular Sciences, University of Edinburgh, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK. jehangirdin@hotmail.com
authors.forename: Jehangir N
authors.initials: JN
authors.lastname: Din
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Archer
authors.forename: Scott A
authors.initials: SA
authors.lastname: Harding
authors.forename: Jaydeep
authors.initials: J
authors.lastname: Sarma
authors.forename: Karin
authors.initials: K
authors.lastname: Lyall
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Flapan
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
mesh_terms: D000328:Adult; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D010974:Platelet Aggregation / Q000187:drug effects; D010991:Plethysmography; D011446:Prospective Studies; D012907:Smoking / Q000009:adverse effects* / Q000097:blood / Q000503:physiopathology; D062789:Tobacco Products; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D015525:Fatty Acids, Omega-3