TY - JOUR
T1 - Emerging mechanisms for growth and protection of the vasculature by cytochrome P450-derived products of arachidonic acid and other eicosanoids
AU - Medhora, Meetha
AU - Dhanasekaran, Anuradha
AU - Gruenloh, Stephanie K.
AU - Dunn, Laurel K.
AU - Gabrilovich, Michael
AU - Falck, John R.
AU - Harder, David R.
AU - Jacobs, Elizabeth R.
AU - Pratt, Phillip F.
N1 - Funding Information:
We thank all members in the laboratories of Drs. Elizabeth Jacobs, David Harder, Andrey Sorokin and Meetha Medhora for their help and support. The recombinant adenovirus expressing FRNK was from the Virus Vector Core Facility, University of North Carolina, Chapel Hill, while GFP expressing vector was prepared by Xinnan Niu at the Viral Core Facility, Medical College of Wisconsin, Milwaukee. Funding was provided by NIH/NHLBI grants HL069996 (M.M.), 49294 (E.R.J.) and 68627 (E.R.J.), NIHGM31278 (J.R.F.) and the Robert A. Welch Foundation (J.R.F.) and is gratefully acknowledged.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - COX inhibitors
KW - Cardioprotection
KW - DDMS
KW - HET0016
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U2 - 10.1016/j.prostaglandins.2006.05.025
DO - 10.1016/j.prostaglandins.2006.05.025
M3 - Review article
C2 - 17164129
AN - SCOPUS:33845313333
SN - 1098-8823
VL - 82
SP - 19
EP - 29
JO - Journal of Lipid Mediators and Cell Signalling
JF - Journal of Lipid Mediators and Cell Signalling
IS - 1-4
ER -