Interferon-gamma produced by bone marrow-derived cells attenuates atherosclerotic lesion formation in LDLR-deficient mice.

Tamikazu Niwa, Hisayasu Wada, Hazuki Ohashi, Naoki Iwamoto, Hirotoshi Ohta, Hirokazu Kirii, Hidehiko Fujii, Kuniaki Saito, Mitsuru Seishima

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

BACKGROUND: We evaluated the role of IFN-gamma produced by bone marrow-derived cells in atherogenesis in LDLR(-/-) mice using bone marrow transplantation (BMT). METHODS AND 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.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalJournal of atherosclerosis and thrombosis
Volume11
Issue number2
DOIs
Publication statusPublished - 2004

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

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