J. Nilsson et al., IMMUNIZATION WITH HOMOLOGOUS OXIDIZED LOW-DENSITY-LIPOPROTEIN REDUCESNEOINTIMAL FORMATION AFTER BALLOON INJURY IN HYPERCHOLESTEROLEMIC RABBITS, Journal of the American College of Cardiology, 30(7), 1997, pp. 1886-1891
Objectives. In this study we tested the hypothesis that immunization w
ith homologous oxidized low density lipoprotein (oxLDL) would inhibit
the neointimal response to balloon injury in hypercholesterolemic rabb
its, Background. Immunization with homologous oxLDL has been shown to
markedly reduce aortic atherosclerosis in LDL receptor-deficient as we
ll as cholesterol-fed rabbits; however, the effect of this strategy on
the balloon injury-induced neointimal lesion is unknown, Methods, New
Zealand White rabbits were immunized with 280 mu g of homologous nati
ve LDL (n = 5), copper-oxidized LDL (n = 5) or phosphate buffer as con
trol (n = 5) and fed a 1% cholesterol diet, Rabbits were reimmunized a
fter 3 weeks, and balloon injury of the right ileofemoral artery was p
erformed 1 week later, Four weeks after balloon injury, rabbits were k
illed, and the neointimal lesion area was measured by computerized mor
phometry after perfusion fixation of the arteries, Circulating antibod
ies against oxLDL were measured by enzyme-linked immunosorbent assay,
Results, In comparison with the control animals, those immunized with
oxLDL had a 58% reduction in the neointimal area (0.53 +/- 0.13 vs, 1.
27 +/- 0.26 mm(2); p = 0.01), The group immunized with native LDL had
a 19% reduction in the neointimal area compared with the control group
(p = NS), Circulating cholesterol levels and antibody titers against
oxLDL were comparable in the three groups, There was a trend toward re
duced immunoreactivity for T cells and oxLDL in the neointima of oxLDL
-immunized animals, Conclusions. Hypercholesterolemic rabbits immunize
d with homologous oxLDL have a markedly reduced neointimal area after
balloon injury despite severe hypercholesterolemia. Together with prev
ious work, these data suggest that an immunization strategy (vaccinati
on) against atherosclerosis and restenosis warrants further investigat
ion. (C) 1997 by the American College of Cardiology.