PT  - JOURNAL ARTICLE
AU  - Iolanda M. Fierro
AU  - Jeffery L. Kutok
AU  - Charles N. Serhan
TI  - Novel Lipid Mediator Regulators of Endothelial Cell Proliferation and Migration: Aspirin-Triggered-15<em>R</em>-Lipoxin A<sub>4</sub> and Lipoxin A<sub>4</sub>
AID  - 10.1124/jpet.300.2.385
DP  - 2002 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 385--392
VI  - 300
IP  - 2
4099  - http://jpet.aspetjournals.org/content/300/2/385.short
4100  - http://jpet.aspetjournals.org/content/300/2/385.full
SO  - J Pharmacol Exp Ther2002 Feb 01; 300
AB  - Proliferative states such as chronic inflammation, ischemic diseases, and cancer are often accompanied by intense angiogenesis, a highly orchestrated process involving vessel sprouting, endothelial cell migration, proliferation, and maturation. Aspirin-triggered lipoxins (ATLs), the 15R enantiomeric counterparts of lipoxins (LXs), are endogenous mediators generated during multicellular responses that display potent immunomodulatory actions. Herein, we report a novel action for the ATL stable analog 15-epi-16-(para-fluoro)-phenoxy-lipoxin A4(denoted ATL-1), which proved to be a potent inhibitor of angiogenesis. This ATL inhibited endothelial cell proliferation in the 1 to 10 nM range by ∼50% in cells stimulated with either vascular endothelial growth factor (VEGF) at 3 ng/ml or leukotriene D4 at 10 nM. In addition, ATL-1 (in a 10–100 nM range) inhibited VEGF (3 ng/ml)-induced endothelial cell chemotaxis. In a granuloma in vivo model of inflammatory angiogenesis, ATL-1 treatment (10 μg/mouse) reduced by ∼50% the angiogenic phenotype, as assessed by both vascular casting and fluorescence. Together, these results identify a novel and potent previously unappreciated action of aspirin-triggered 15-epi-LX. The American Society for Pharmacology and Experimental Therapeutics