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CYP4A metabolites of arachidonic acid and VEGF are mediators of skeletal muscle angiogenesis. Am J Physiol Heart Circ Physiol 2003 May;284(5):H1528-35 PMID: 12521947


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.

Author List

Amaral SL, Maier KG, Schippers DN, Roman RJ, Greene AS


Andrew S. Greene PhD Interim Vice Chair, Chief, Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alkane 1-Monooxygenase
Arachidonic Acid
Cytochrome P-450 Enzyme System
Electric Stimulation
Endothelial Growth Factors
Enzyme Inhibitors
Hydroxyeicosatetraenoic Acids
Intercellular Signaling Peptides and Proteins
Mixed Function Oxygenases
Muscle, Skeletal
Neovascularization, Physiologic
Rats, Sprague-Dawley
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors

View this publication's entry at the Pubmed website PMID: 12521947
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