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

In the previous study, we generated mice lacking thromboxane A2 receptor (TP) and apolipoprotein E, apoE−/−TP−/− mice, and reported that the double knockout mice developed markedly smaller atherosclerotic lesions than those in apoE−/− mice. To investigate the mechanism responsible for reduced atherosclerosis in apoE−/−TP−/− 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−/− and in apoE−/−TP−/− 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−/− or apoE−/−TP−/− mice to either apoE−/− or apoE−/−TP−/− mice after sublethal irradiation. After 12 weeks with high fat diet, we analyzed the atherosclerotic lesion of aortic sinus. When the BM from apoE−/− or apoE−/−TP−/− mice was transplanted to apoE−/− mice, the lesion size was almost the same as that of apoE−/− mice without BM transplantation. In contrast, when the BM from apoE−/− or apoE−/−TP−/− mice was transplanted to apoE−/−TP−/− mice, the lesion size was markedly reduced. These results indicate that the protection of atherogenesis in TP−/− mice is not associated with TP in BM-derived cells.