PMID- 23238663 OWN - NLM STAT- MEDLINE DCOM- 20130918 LR - 20211021 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 36 IP - 4 DP - 2013 Apr TI - Platelet redox balance in diabetic patients with hypertension improved by n-3 fatty acids. PG - 998-1005 LID - 10.2337/dc12-0304 [doi] AB - 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. RESEARCH DESIGN AND 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. FAU - McDonald, Denise M AU - McDonald DM AD - Centre for Vision and Vascular Science, Queen's University Belfast, Belfast, UK. d.mcdonald@qub.ac.uk FAU - O'Kane, Fiona AU - O'Kane F FAU - McConville, Maeve AU - McConville M FAU - Devine, Adrian B AU - Devine AB FAU - McVeigh, Gary E AU - McVeigh GE LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20121213 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Fatty Acids, Omega-3) RN - 11062-77-4 (Superoxides) RN - 27415-26-5 (8-epi-prostaglandin F2alpha) RN - B7IN85G1HY (Dinoprost) SB - IM MH - Aged MH - Blood Platelets/*metabolism MH - Cross-Over Studies MH - Diabetes Mellitus, Type 2/*blood/*diet therapy MH - Dinoprost/analogs & derivatives/metabolism MH - Double-Blind Method MH - Fatty Acids, Omega-3/*therapeutic use MH - Female MH - Humans MH - Hypertension/*blood/*diet therapy MH - Male MH - Middle Aged MH - Oxidation-Reduction MH - Superoxides/metabolism PMC - PMC3609528 EDAT- 2012/12/15 06:00 MHDA- 2013/09/21 06:00 PMCR- 2014/04/01 CRDT- 2012/12/15 06:00 PHST- 2012/12/15 06:00 [entrez] PHST- 2012/12/15 06:00 [pubmed] PHST- 2013/09/21 06:00 [medline] PHST- 2014/04/01 00:00 [pmc-release] AID - dc12-0304 [pii] AID - 0304 [pii] AID - 10.2337/dc12-0304 [doi] PST - ppublish SO - Diabetes Care. 2013 Apr;36(4):998-1005. doi: 10.2337/dc12-0304. Epub 2012 Dec 13.