Caveolin-1 regulates the anti-atherogenic properties of macrophages
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Atherosclerosis is a complex disease initiated by the vascular accumulation of lipoproteins in the sub-endothelial space, followed by the infiltration of monocytes into the arterial intima. Caveolin-1 (Cav-1) plays an essential role in the regulation of cellular cholesterol metabolism and of various signaling pathways. In order to study specifically the role of macrophage Cav-1 in atherosclerosis, we used Cav-1 −/− Apoe −/− mice and transplanted them with bone marrow (BM) cells obtained from Cav-1 +/+ Apoe −/− or Cav-1 −/− Apoe −/− mice and vice versa. We found that Cav-1 +/+ mice harboring Cav-1 −/− BM-derived macrophages developed significantly larger lesions than Cav-1 +/+ mice harboring Cav-1 +/+ BM-derived macrophages. Cav-1 −/− macrophages were more susceptible to apoptosis and more prone to induce inflammation. The present study provides clear evidence that the absence of Cav-1 in macrophage is pro-atherogenic, whereas its absence in endothelial cells protects against atherosclerotic lesion formation. These findings demonstrate the cell-specific role of Cav-1 during the development of this disease.
KeywordsCaveolin Caveolae Macrophage Atherosclerosis Lipoproteins Mouse
The authors thank Dr. Iset Medina Vera for her technical support. P.G.F. was supported by grants from the Jane Barsumian/Mary Lyons Trust and the W.W. Smith Trust Fund. M.P.L. was supported by grants from the National Institutes of Health and the American Heart Association.
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