title: CYP4A metabolites of arachidonic acid and VEGF are mediators of skeletal muscle angiogenesis.
abstract: Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis induced by electrical stimulation in skeletal muscle. Less is known about the role of arachidonic acid metabolites in the control of growth of blood vessels in vivo. The present study examined the role of 20-hydroxyeicosatetraenoic acid (20-HETE) on the angiogenesis induced by electrical stimulation in skeletal muscle. The tibialis anterior and extensor digitorum longus muscles of rats were stimulated for 7 days. Electrical stimulation significantly increased the 20-HETE formation and angiogenesis in the muscles, which was blocked by chronic treatment with N-hydroxy-N'-(4-butyl-2-methylphenol)formamidine (HET0016) or 1-aminobenzotriazole (ABT). Chronic treatment with either HET0016 or ABT did not block the increases in VEGF protein expression in both muscles. To analyze the role of VEGF on 20-HETE formation, additional rats were treated with VEGF-neutralizing antibody (VEGF Ab). VEGF Ab blocked the increases of 20-HETE formation induced by stimulation. These results place 20-HETE in the downstream signaling pathway for angiogenesis and show that both VEGF and 20-HETE are involved in the angiogenesis induced by electrical stimulation in skeletal muscle.
authors.affiliation: Department of Physiology and Biotechnology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Amaral
authors.forename: Kristopher G
authors.initials: KG
authors.lastname: Maier
authors.forename: Daniela N
authors.initials: DN
authors.lastname: Schippers
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greene
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004558:Electric Stimulation; D016228:Endothelial Growth Factors / Q000276:immunology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000578:Amidines; D000906:Antibodies; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; C000708209:HET0016; D006893:Hydroxyeicosatetraenoic Acids; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A