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We fed young male pigs one of three diets differing in n-6 and n-3 polyunsaturated fatty acids (PUFA) linoleic acid (LA, 18:2n-6) and \u03b1-linolenic acid (ALA, 18:3n-3) for 30 days. Cardiac membrane phospholipid fatty acids, phospholipase A<jats:sub>2<\/jats:sub>(PLA<jats:sub>2<\/jats:sub>) isoform activities, and cyclooxygenase (COX)-1 and -2 and 5-lipoxygenase (5-LO) expression were measured. The low PUFA diet (% energy, 1.2% LA+0.06% ALA) increased arachidonic acid (AA) and decreased eicosapentaenoic acid (EPA) in heart membranes and increased Ca<jats:sup>2+<\/jats:sup>-independent iPLA<jats:sub>2<\/jats:sub>activity, COX-2 expression, and activation of 5-LO. Increasing dietary ALA while keeping LA constant (1.4% LA+1.2% ALA) decreased the heart membrane AA, increased EPA, and prevented proinflammatory enzyme activation. However, regardless of high ALA, high dietary LA (11.6% LA and 1.2% ALA) decreased EPA and led to a high heart membrane AA, and Ca<jats:sup>2+<\/jats:sup>-dependent cPLA<jats:sub>2<\/jats:sub>with a marked increase in nitrosative stress. Our results suggest that the potential cardiovascular benefit of ALA is achieved only when dietary LA is reduced concomitantly rather than fed with high LA diet. The increased nitrosative stress in the unstressed heart with high dietary LA suggests that biomarkers of nitrosative stress may offer a useful early marker of the effects of dietary fat on oxidative tissue stress.<\/jats:p>","DOI":"10.1152\/ajpheart.00324.2007","type":"journal-article","created":{"date-parts":[[2007,8,25]],"date-time":"2007-08-25T00:53:29Z","timestamp":1188003209000},"page":"H2919-H2927","source":"Crossref","is-referenced-by-count":37,"title":["Cardiac proinflammatory pathways are altered with different dietary n-6 linoleic to n-3 \u03b1-linolenic acid ratios in normal, fat-fed pigs"],"prefix":"10.1152","volume":"293","author":[{"given":"Sanjoy","family":"Ghosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Novak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M.","family":"Innis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(02)00358-X"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/121.6.771"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03413-0"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.5.C1424"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.03.021"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Boulos C, Jiang H, Balazy M.Diffusion of peroxynitrite into the human platelet inhibits cyclooxygenase via nitration of tyrosine residues.J Pharmacol Exp Ther293: 222\u2013229, 2000.","DOI":"10.1016\/S0022-3565(24)39223-7"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.1.88"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(02)00144-4"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(02)00286-X"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500384-JLR200"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1007\/BF00227899"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"de Lorgeril M, Salen P.The Mediterranean diet in secondary prevention of coronary heart disease.Clin Invest Med29: 154\u2013158, 2006.","DOI":"10.1159\/000097870"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"de Lorgeril M, Salen P.The Mediterranean-style diet for the prevention of cardiovascular diseases.Public Health Nutr9: 118\u2013123, 2006.","DOI":"10.1079\/PHN2005933"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.01.034"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00747-X"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2004.06.002"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/0952-3278(88)90023-3"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2004.06.013"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.07.021"},{"key":"R20A","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)07072-5"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2001.10719008"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1139\/y94-214"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/123.suppl_2.386"},{"key":"R24","unstructured":"Innis SM.Essential fatty acid metabolism during early development. 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