| First Author | Aarup A | Year | 2016 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 36 |
| Issue | 9 | Pages | 1782-90 |
| PubMed ID | 27444197 | Mgi Jnum | J:246461 |
| Mgi Id | MGI:5920778 | Doi | 10.1161/ATVBAHA.116.307830 |
| Citation | Aarup A, et al. (2016) Hypoxia-Inducible Factor-1alpha Expression in Macrophages Promotes Development of Atherosclerosis. Arterioscler Thromb Vasc Biol 36(9):1782-90 |
| abstractText | OBJECTIVE: Atherosclerotic lesions contain hypoxic areas, but the pathophysiological importance of hypoxia is unknown. Hypoxia-inducible factor-1alpha (HIF-1alpha) is a key transcription factor in cellular responses to hypoxia. We investigated the hypothesis that HIF-1alpha has effects on macrophage biology that promotes atherogenesis in mice. APPROACH AND RESULTS: Studies with molecular probes, immunostaining, and laser microdissection of aortas revealed abundant hypoxic, HIF-1alpha-expressing macrophages in murine atherosclerotic lesions. To investigate the significance of macrophage HIF-1alpha, Ldlr(-/-) mice were transplanted with bone marrow from mice with HIF-1alpha deficiency in the myeloid cells or control bone marrow. The HIF-1alpha deficiency in myeloid cells reduced atherosclerosis in aorta of the Ldlr(-/-) recipient mice by approximately 72% (P=0.006).In vitro, HIF-1alpha-deficient macrophages displayed decreased differentiation to proinflammatory M1 macrophages and reduced expression of inflammatory genes. HIF-1alpha deficiency also affected glucose uptake, apoptosis, and migratory abilities of the macrophages. CONCLUSIONS: HIF-1alpha expression in macrophages affects their intrinsic inflammatory profile and promotes development of atherosclerosis. |
