Epoxygenase-driven angiogenesis in human lung microvascular endothelial cells. Am J Physiol Heart Circ Physiol 2003 Jan;284(1):H215-24
Date
10/22/2002Pubmed ID
12388259DOI
10.1152/ajpheart.01118.2001Scopus ID
2-s2.0-0037230201 (requires institutional sign-in at Scopus site) 109 CitationsAbstract
Angiogenesis is one of the most recent physiological functions attributed to products of cytochrome P-450 (CYP450) enymes. To test this at a molecular level in human cells, we used a cloned cDNA for the human endothelial enzyme CYP450 2C9 (CYP2C9) to study growth as well as differentiation of human microvascular endothelial cells from the lung (HMVEC-L). Using adenoviral vectors overexpressing mRNA for CYP2C9, we show that the presence of CYP2C9 doubles thymidine incorporation and stimulates proliferation of primary cultures of endothelial cells compared with Ad5-GFP (control) in 24 h. In addition, there is a significant increase of tube formation in Matrigel after infection of HMVEC-L with Ad5-2C9 than with Ad5-GFP. More interestingly, Ad5-2C9 expressing the antisense product of CYP2C9 (2C9AS) inhibited tube formation compared with both Ad5-GFP as well as the Ad5-2C9 constructs. Finally, we tested the most abundant arachidonic acid metabolite of CYP2C9, 14,15-epoxyeicosatrienoic acid, which induced angiogenesis in vivo when embedded in Matrigel plugs and implanted in adult rats. These data support an important role for CYP2C9 in promoting angiogenesis.
Author List
Medhora M, Daniels J, Mundey K, Fisslthaler B, Busse R, Jacobs ER, Harder DRAuthor
Kavita Ratarasarn MD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAdenoviridae
Animals
Aryl Hydrocarbon Hydroxylases
Cells, Cultured
Cytochrome P-450 CYP2C9
DNA
Endothelium, Vascular
Gene Transfer Techniques
Genetic Vectors
Humans
Microcirculation
Neovascularization, Physiologic
Pulmonary Circulation
Rats
Rats, Sprague-Dawley
Vasodilator Agents
