Interferon-gamma produced by bone marrow-derived cells attenuates atherosclerotic lesion formation in LDLR-deficient mice.
BACKGROUND
We evaluated the role of IFN-gamma produced by bone marrow-derived cells in atherogenesis in LDLR(-/-) mice using bone marrow transplantation (BMT).


RESULTS
We generated IFN-gamma-deficient bone marrow transplanted LDLR(-/- )mice (IFN-gamma(-/-) BMT mice), and compared them with controls (IFN-gamma(+/+) BMT mice). These mice were fed a high-fat diet (HFD). Plasma total cholesterol and triglyceride levels did not differ between these two groups. After 6 weeks of HFD feeding, the atherosclerotic lesions of IFN-gamma(-/-) BMT mice were larger than those of IFN-gamma(+/+) BMT mice at the aortic sinus, aortic arch and abdominal aorta. After 12 weeks of HFD feeding, the significant differences between the two groups disappeared except for the atherosclerotic lesion in the aortic sinus. MOMA2, CD4, CD8 or alpha-smooth muscle actin-positive cells were detected in the atherosclerotic lesions. The cellular composition of the lesions was identical between the two groups, but the cellular density showed decreased concomitant with the increased extracellular matrix deposition in IFN-gamma(-/- )BMT mice.


CONCLUSIONS
These findings demonstrate that IFN-gamma produced by bone marrow-derived cells delays the progression of atherosclerosis without any effect on plasma lipids, and this suppression may be due to decreased extracellular matrix deposition.
Niwa
Tamikazu
T
Department of Clinical Laboratory Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan.
Wada
Hisayasu
H
Ohashi
Hazuki
H
Iwamoto
Naoki
N
Ohta
Hirotoshi
H
Kirii
Hirokazu
H
Fujii
Hidehiko
H
Saito
Kuniaki
K
Seishima
Mitsuru
M
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D017931:DNA Primers; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology*; D015996:Survival Rate; D014280:Triglycerides / Q000097:blood
D017931:DNA Primers; D011973:Receptors, LDL; D014280:Triglycerides; D007371:Interferon-gamma; D002784:Cholesterol