title: Platelet redox balance in diabetic patients with hypertension improved by n-3 fatty acids.
abstract: OBJECTIVE
  Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease, largely as a result of defective production of cardioprotective nitric oxide and a concomitant rise in oxidative stress. Dietary interventions that could reverse this trend would be extremely beneficial. Here we investigated whether dietary n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation positively affected platelet nitroso-redox imbalance.
  
  
  METHODS
  We randomized hypertensive T2DM patients (T2DM HT; n = 22) and age-and-sex matched hypertensive study participants without diabetes (HT alone; n = 23) in a double-blind, crossover fashion to receive 8 weeks of n-3 PUFAs (1.8 g eicosapentaenoic acid and 1.5 g docosahexaenoic acid) or identical olive oil capsules (placebo), with an intervening 8-week washout period. Platelet nitrite and superoxide were measured and compared before and after treatment; 8-isoprostane was determined by ELISA and subcellular compartmentalization of the NAD(P)H oxidase subunit p47-phox examined by Western blotting.
  
  
  RESULTS
  The n-3 PUFA supplementation reduced 8-isoprostane and superoxide levels in platelets from T2DM HT, but not HT alone, participants, without effect on nitrite production. This coincided with a significant decrease in p47-phox membrane localization and a similar reduction in superoxide to that achieved with apocynin. At baseline, a subcohort of T2DM HT and HT alone participants showed evidence of nitric oxide synthase (NOS)-derived superoxide production, indicating defective enzymatic activity. This was reversed significantly in T2DM HT participants after treatment, demonstrating improved NOS function.
  
  
  CONCLUSIONS
  Our finding that n-3 PUFAs diminish platelet superoxide production in T2DM HT patients in vivo suggests a therapeutic role for these agents in reducing the vascular-derived oxidative stress associated with diabetes.
authors.affiliation: Centre for Vision and Vascular Science, Queen's University Belfast, Belfast, UK. d.mcdonald@qub.ac.uk
authors.forename: Denise M
authors.initials: DM
authors.lastname: McDonald
authors.forename: Fiona
authors.initials: F
authors.lastname: O'Kane
authors.forename: Maeve
authors.initials: M
authors.lastname: McConville
authors.forename: Adrian B
authors.initials: AB
authors.lastname: Devine
authors.forename: Gary E
authors.initials: GE
authors.lastname: McVeigh
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000178:diet therapy*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000178:diet therapy*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D013481:Superoxides / Q000378:metabolism
chemical_list: D015525:Fatty Acids, Omega-3; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost