| First Author | Bouchareychas L | Year | 2015 |
| Journal | Cardiovasc Res | Volume | 108 |
| Issue | 1 | Pages | 111-23 |
| PubMed ID | 26092098 | Mgi Jnum | J:260862 |
| Mgi Id | MGI:6141468 | Doi | 10.1093/cvr/cvv177 |
| Citation | Bouchareychas L, et al. (2015) Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE. Cardiovasc Res 108(1):111-23 |
| abstractText | AIMS: Macrophage apoptosis is a prominent feature of atherosclerosis, yet whether cell death-protected macrophages would favour the resolution of already established atherosclerotic lesions, and thus hold therapeutic potential, remains unknown. METHODS AND RESULTS: We irradiated then transplanted into Apoe(-/-) or LDLr(-/-) recipient mice harbouring established atherosclerotic lesions, bone marrow cells from mice displaying enhanced macrophage survival through overexpression of the antiapoptotic gene hBcl-2 (Mo-hBcl2 Apoe(-/-) or Mo-hBcl2 Apoe(+/+) LDLr(-/-)). Both recipient mice exhibited decreased lesional apoptotic cell content and reduced necrotic areas when repopulated with Mo-hBcl2 mouse-derived bone marrow cells. In contrast, only LDLr(-/-) recipients showed a reduction in plasma cholesterol levels and in atherosclerotic lesions. The absence of significant reduction of plasma cholesterol levels in the context of apoE deficiency highlighted macrophage-derived apoE as key in both the regulation of plasma and tissue cholesterol levels and the progression of pre-existing lesion. Accordingly, hBcl2 expression in macrophages was associated with larger pools of Kupffer cells and Ly-6C(low) monocytes, both high producers of apoE. Additionally, increased Kupffer cells population was associated with improved clearance of apoptotic cells and modified lipoproteins. CONCLUSION: Collectively, these data show that promoting macrophage survival provides a supplemental source of apoE, which hinders pre-existing plaque progression. |
