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Title: Protection of atherogenesis in thromboxane A2 receptor-deficient mice is not associated with thromboxane A2 receptor in bone marrow-derived cells

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [1];  [1];  [3];  [3];  [4];  [1]
  1. Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)
  2. Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)
  3. Department of Cell Biology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)
  4. Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)

In the previous study, we generated mice lacking thromboxane A2 receptor (TP) and apolipoprotein E, apoE{sup -/-}TP{sup -/-} mice, and reported that the double knockout mice developed markedly smaller atherosclerotic lesions than those in apoE{sup -/-} mice. To investigate the mechanism responsible for reduced atherosclerosis in apoE{sup -/-}TP{sup -/-} mice, we examined the role of TP in bone marrow (BM)-derived cells in the development of the atherosclerotic lesions. When we compared the function of macrophages in apoE{sup -/-} and in apoE{sup -/-}TP{sup -/-} mouse in vitro, there was no difference in the expression levels of cytokines and chemokines after stimulation with lipopolysaccharide. We then transplanted the BM from either apoE{sup -/-} or apoE{sup -/-}TP{sup -/-} mice to either apoE{sup -/-} or apoE{sup -/-}TP{sup -/-} mice after sublethal irradiation. After 12 weeks with high fat diet, we analyzed the atherosclerotic lesion of aortic sinus. When the BM from apoE{sup -/-} or apoE{sup -/-}TP{sup -/-} mice was transplanted to apoE{sup -/-} mice, the lesion size was almost the same as that of apoE{sup -/-} mice without BM transplantation. In contrast, when the BM from apoE{sup -/-} or apoE{sup -/-}TP{sup -/-} mice was transplanted to apoE{sup -/-}TP{sup -/-} mice, the lesion size was markedly reduced. These results indicate that the protection of atherogenesis in TP{sup -/-} mice is not associated with TP in BM-derived cells.

OSTI ID:
20857937
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 351, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2006.10.121; PII: S0006-291X(06)02364-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English