Fish oil supplementation prevents neointima formation in nonhypercholesterolemic balloon-injured rabbit carotid artery by reducing medial and adventitial cell activation
E. Faggin et al., Fish oil supplementation prevents neointima formation in nonhypercholesterolemic balloon-injured rabbit carotid artery by reducing medial and adventitial cell activation, ART THROM V, 20(1), 2000, pp. 152-163
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.