Inhibition of phenylephrine-induced cardiac hypertrophy by docosahexaenoic acid

Rafat A. Siddiqui, Saame Raza Shaikh, Richard Kovacs, William Stillwell, Gary Zaloga

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Many of the cardiovascular benefits of fish oil result from the antiarrhythmic actions of the n-3 polyunsaturated lipids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The beneficial effects of DHA/EPA in patients with coronary artery disease and myocardial infarction may also result from modulation of the myocardial hypertrophic response. Hypertrophy was assessed in neonatal cardiomyocytes exposed to phenylephrine (PE) by measuring cell surface area, total protein synthesis (14C leucine incorporation), and the organization of sarcomeric α-actinin and by monitoring expression of atrial natriuretic factor (ANF). We report that PE induced a twofold increase in cell surface area and protein synthesis in cardiomyocytes. The hypertrophied cardiomyocytes also exhibited increased expression of ANF in perinuclear regions and organization of sarcomeric α-actinin into classical z-bands. Treatment of cardiomyocytes with 5 μM DHA effectively prevented PE-induced hypertrophy as shown by inhibition of surface area expansion and protein synthesis, inhibition of ANF expression, and prevention of α-actinin organization into z-bands. DHA treatment prevented PE-induced activation of Ras and Raf-1 kinase. The upstream inhibition of Ras → Raf-1 effectively prevented translocation and nuclear localization of phosphorylated extracellularly regulated kinase 1 and 2 (Erk1/2). These effects consequently led to inhibition of nuclear translocation, and hence, activation of the downstream signaling enzyme p90 ribosomal S6 kinase (p90rsk). These results indicate that PE-induced cardiac hypertrophy can be minimized by DHA. Our results suggest that inhibition of Ras → Raf-1 → Erk1/2 → p90rsk → hypertrophy is one possible pathway by which DHA can inhibit cardiac hypertrophy. In vivo studies are needed to confirm these in vitro effects of DHA.

Original languageEnglish (US)
Pages (from-to)1141-1159
Number of pages19
JournalJournal of Cellular Biochemistry
Volume92
Issue number6
DOIs
StatePublished - Dec 1 2004

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Keywords

  • Cardiomyocytes
  • Docosahexaenoic acid
  • Erk1/2
  • Protein synthesis
  • Raf
  • Ras

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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