Fish oil supplementation prevents neointima formation in nonhypercholesterolemic balloon-injured rabbit carotid artery by reducing medial and adventitial cell activation

We asked whether balloon-injured neointima formation in the presence of hig h/low serum cholesterol (CT) levels might be affected by dietary supplement ation with fish oil (FO). To test this hypothesis, we examined the differen tiation, proliferation, or apoptosis profile of smooth muscle cell (SMC) an d adventitial cell response to a mild injury induced via a Fogarty catheter in the carotid artery of adult rabbits that had been fed a standard chow o r 0.5% CT-enriched diet starting 4 weeks before the lesion. One week before surgery, animals received FO supplementation. This regimen was continued f or the following 3 weeks. The effect of FO on the early proliferative/migra tory response of carotid SMCs was also examined in 2- and 7-day-injured nor mocholesterolemic rabbits. As controls, animals subjected to 3-week endothe lial injury and animals kept on a 7-week CT diet were used. Carotid cryosec tions from the various animal groups were evaluated for morphometry (image analysis), differentiation (immunofluorescence with monoclonal antibodies s pecific for smooth muscle markers, ie, myosin isoforms, SM22, and fibronect in), proliferation (bromodeoxyuridine incorporation), and apoptosis (termin al deoxynucleotidyl transferase-mediated dUTP nick end labeling). FO treatm ent significantly reduced the development of intimal thickening in normocho lesterolemic rabbits but had no efficacy in the presence of relatively high er serum CT levels. At day 2 (adventitia) and day 7 (neointima, media, and adventitia), the proliferation index of SMCs in FO-treated injured rabbits was markedly lower than in untreated injured controls. Concomitantly with t he antiproliferative effect, FO was able to decrease the size of 2 cell typ es involved in the cell growth response to endothelial injury, namely, the "fetal-type" medial SMC subpopulation and the fibroblast-derived adventitia l myofibroblasts. Thus, in our experimental conditions, a low CT level is a permissive condition for FO to prevent neointima formation to a considerab le extent. This event is attributable to the early postinjury effect of FO on SMC/adventitial cell proliferation/differentiation patterns.