Influence of interferon-gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse.
OBJECTIVE
The aim of this study was to investigate the influence of interferon-gamma (IFN-gamma) on atherosclerosis in low density lipoprotein receptor (LDLR)-null mice.


RESULTS
We cross-bred IFN-gamma-deficient mice with LDLR-null mice and analyzed lipoprotein profiles and atherosclerosis in the compound mutant progeny after 8 and 20 weeks on a cholesterol-enriched diet. IFN-gamma deficiency did not affect serum cholesterol levels or lipoprotein profiles, but it did affect the extent and phenotype of atherosclerosis. Atherosclerotic lesions in IFN-gamma-deficient mice were reduced by 75% in the aortic arch and by 46% in the descending aorta compared with control mice after 8 weeks on the diet. After 20 weeks, arch lesions were reduced by 43%, and descending aorta lesions were reduced by 65% in IFN-gamma-deficient mice compared with controls. At 8 weeks, percent lesional macrophage and smooth muscle content was significantly less in the IFN-gamma-deficient mice, but not at 20 weeks. Although there were fewer class II major histocompatibility complex-positive cells in the lesions of IFN-gamma-deficient animals compared with controls, class II major histocompatibility complex expression on endothelial cells overlying lesions persisted in the absence of IFN-gamma.


CONCLUSIONS
These data provide direct evidence that IFN-gamma influences atherosclerosis development and phenotype in the LDLR-deficient mouse, independent of changes in blood lipoprotein profiles.
Buono
Chiara
C
Immunology Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA.
Come
Carolyn E
CE
Stavrakis
George
G
Maguire
Graham F
GF
Connelly
Philip W
PW
Lichtman
Andrew H
AH
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D007958:Leukocyte Count; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D011973:Receptors, LDL / Q000172:deficiency*; D013601:T-Lymphocytes / Q000378:metabolism
D016207:Cytokines; D008074:Lipoproteins; D011973:Receptors, LDL; D007371:Interferon-gamma