Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cardiovascular Research Année : 2015

Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE

Résumé

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 (Mø-hBcl2 Apoe(-/-) or Mø-hBcl2 Apoe(+/+) LDLr(-/-)). Both recipient mice exhibited decreased lesional apoptotic cell content and reduced necrotic areas when repopulated with Mø-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.

Dates et versions

hal-03798228 , version 1 (05-10-2022)

Identifiants

Citer

Laura Bouchareychas, John Pirault, Flora Saint-Charles, Virginie Deswaerte, Tiphaine Le Roy, et al.. Promoting macrophage survival delays progression of pre-existing atherosclerotic lesions through macrophage-derived apoE. Cardiovascular Research, 2015, 108 (1), pp.111-123. ⟨10.1093/cvr/cvv177⟩. ⟨hal-03798228⟩
29 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More