Abstract
Purpose:
The purpose of this study is to determine if sterculic acid (SA) and sterculia oil (SO) will inhibit 7-ketocholesterol (7KCh)-mediated inflammation and angiogenesis in vivo.
Methods:
An angiogenesis model was developed in rats by placing wafers containing 7KCh in the anterior chamber of the eye. The wafers were prepared using a mixture of poly (2-hydroxyethymethacrylate) and polyethylene glycol 20K (50:50 w/w). The appropriate amounts of 7KCh, SA and/or SO were then added to the mixture. India ink was added to the wafers to ensure proper mixing of all the components. Corneal vessel growth was imaged at 7, 10, 14, and 21 days after implantation by fluorescein angiography using a dissecting microscope equipped with a fluorescent lamp. Neovessels were quantified by area measurement using the Nikon NIS elements software.
Results:
Four different 7KCh concentrations were used in the wafers, 5%, 7%, 10% and 15% (w/w). All concentrations of 7KCh consistently induced corneal angiogenesis. Peak neovessel growth was observed for all concentrations between 7 and 10 days after implantation. Neovessel area regressed thereafter. Various combinations of 7KCh and SA were tested (0.1, 0.5, 1, 2.5, 5% SA + 5% 7KCh; 10% SA + 10% 7KCh). All concentrations of SA reduced 7KCh-mediated corneal neovascularization. SA significantly inhibited 7KCh-mediated angiogenesis at a concentration as low as 0.1% SA with 5% 7KCh (w/w). The reduction in neovessel growth in SA-containing wafers ranged from 30% to 60%. Several combinations of 7KCh and SO were also tested (1% SO + 7% 7KCh, 10% SO + 10% 7KCh). All concentrations of SO reduced 7KCh-mediated corneal neovascularization in all 7KCh concentrations. SO significantly reduced 7KCh-mediated angiogenesis at a concentration as low as 1% SO with 7% 7KCh wafers. The reduction in neovessel growth in SO-containing wafers ranged from 42% to 55%.
Conclusions:
7KCh promotes angiogenesis and inflammation in vivo, while SA and SO effectively antagonizes these effects. Our results further support our hypothesis that chronic 7KCh accumulation could be involved in the development of chronic inflammation and angiogenesis. SA and/or SO may be potential therapeutic agents for the treatment of age-related diseases in which chronic inflammation caused by oxidized lipids play a major role in their pathogenesis (e.g. atherosclerosis and age-related macular degeneration).
Keywords: 609 neovascularization •
583 lipids •
557 inflammation