Emerging mechanisms for growth and protection of the vasculature by cytochrome P450-derived products of arachidonic acid and other eicosanoids

Meetha Medhora, Anuradha Dhanasekaran, Stephanie K. Gruenloh, Laurel K. Dunn, Michael Gabrilovich, John R. Falck, David R. Harder, Elizabeth R. Jacobs, Phillip F. Pratt

Research output: Contribution to journalReview article

39 Scopus citations

Abstract

Arachidonic acid (AA) is an essential fatty acid that is metabolized by cyclooxygenase (COX), lipoxygenase (LOX) or cytochrome P450 (CYP) enzymes to generate eicosanoids which in turn mediate a number of biological activities including regulation of angiogenesis. While much information on the effects of COX and LOX products is known, the physiological relevance of the CYP-derived products of AA are less well understood. CYP enzymes are highly expressed in the liver and kidney, but have also been detected at lower levels in the brain, heart and vasculature. A number of these enzymes, including members of the CYP 4 family, predominantly catalyze conversion of AA to 20-hydroxyeicosatetraenoic acid (20-HETE) while the CYP epoxygenases generate mainly epoxyeicosatrienoic acids (EETs). This review will focus on the emerging roles of inhibitors of eicosanoid production with emphasis on the CYP pathways, in the regulation of angiogenesis and tumor growth. We also discuss current observations describing the protective effects of EETs for survival of the endothelium.

Original languageEnglish (US)
Pages (from-to)19-29
Number of pages11
JournalProstaglandins and Other Lipid Mediators
Volume82
Issue number1-4
DOIs
StatePublished - Jan 1 2007

Keywords

  • Apoptosis
  • COX inhibitors
  • Cardioprotection
  • DDMS
  • HET0016

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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