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Omega‐3 polyunsaturated fatty acids (n‐3 PUFAs) improve survival following myocardial infarction and inhibit phenylephrine‐induced hypertrophy by regulating protein kinase activities
Author(s) -
Siddiqui Rafat,
Ruzmetov Nargiz,
Harvey Kevin,
Stillwell William,
Zaloga Gary
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1016-a
Subject(s) - polyunsaturated fatty acid , medicine , docosahexaenoic acid , endocrinology , myocardial infarction , protein kinase a , muscle hypertrophy , kinase , phenylephrine , camk , biology , fatty acid , biochemistry , blood pressure , autophosphorylation
Epidemiological and clinical data suggest that n‐3 PUFAs decrease sudden death in patients with coronary disease. The objectives of the present study were to confirm the findings from clinical trials using an animal model of myocardial infarction and an in vitro model of cardiac hypertrophy. Animal model of myocardial infarction: A diet high in n‐3 PUFAs was associated with significant improvement in six‐month mortality compared to those on a diet high in n‐6 PUFAs [(86.5% vs 64.9%), p<0.01]. The improved survival in n‐3–fed animals was associated with decreased protein kinase A (PKA) and calcium calmodulin kinase II (CaMKII) activities in hearts by 35–46% (n=5, P<0.05) compared to those of n‐6 animals. We also found that heart‐specific ryanodine receptor 2 phosphorylation, which is regulated by PKA and CaMKII activities, was decreased in the n‐3 PUFAs diet group by ~20% (n=5, P<0.05). Cellular model of hypertrophy: Phenylephrine (PE)‐induced hypertrophy was prevented by docosahexaenoic acid (DHA) as assayed by inhibition of surface area expansion, protein synthesis, ANF expression, and prevention of α‐actinin organization into z‐bands. DHA treatment inhibited Ras and Raf‐1 kinase activation, preventing phosphorylation of Erk1/2, which consequently led to inhibition of p90 ribosomal S6 kinase (p90 rsk ). Therefore, we conclude that decreased protein kinase activity induced by n‐3 PUFAs provides beneficial effects to the cardiovascular system.