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Epoxygenase-driven angiogenesis in human lung microvascular endothelial cells
Meetha Medhora1, John Daniels, Kavita Mundey
1Division of Pulmonary and Critical Care, Department of Medicine, Cardiovascular Center, Medical College of Wisconsin, Milwaukee 53226, USA. medhoram@mcw.edu
American Journal of Physiology. Heart and Circulatory Physiology
|October 22, 2002
Summary
Cytochrome P-450 2C9 (CYP2C9) promotes angiogenesis, the formation of new blood vessels. This enzyme enhances endothelial cell growth, proliferation, and tube formation, with its metabolite driving in vivo angiogenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Vascular Biology
Background:
- Angiogenesis is a critical physiological process.
- Cytochrome P-450 (CYP450) enzymes are increasingly recognized for roles beyond metabolism.
- The specific contribution of CYP450 enzymes to angiogenesis is an emerging area of research.
Purpose of the Study:
- To investigate the role of cytochrome P-450 2C9 (CYP2C9) in angiogenesis at a molecular level.
- To examine the effects of CYP2C9 on human microvascular endothelial cell (HMVEC-L) growth and differentiation.
Main Methods:
- Utilized adenoviral vectors to overexpress CYP2C9 mRNA in HMVEC-L.
- Assessed thymidine incorporation and cell proliferation.
- Evaluated tube formation in Matrigel assays.
- Investigated the effect of a CYP2C9 antisense product (2C9AS).
- Tested the pro-angiogenic potential of 14,15-epoxyeicosatrienoic acid (14,15-EEA) in vivo.
Main Results:
- Overexpression of CYP2C9 doubled thymidine incorporation and stimulated HMVEC-L proliferation.
- CYP2C9 significantly increased tube formation in Matrigel assays.
- The antisense construct (2C9AS) inhibited tube formation.
- The CYP2C9 metabolite, 14,15-EEA, induced angiogenesis in vivo.
Conclusions:
- CYP2C9 plays a significant role in promoting angiogenesis.
- CYP2C9 enhances endothelial cell proliferation and differentiation.
- The metabolite 14,15-EEA contributes to the pro-angiogenic function of CYP2C9.