Format

Send to

Choose Destination
Arterioscler Thromb Vasc Biol. 2016 Sep;36(9):1782-90. doi: 10.1161/ATVBAHA.116.307830. Epub 2016 Jul 21.

Hypoxia-Inducible Factor-1α Expression in Macrophages Promotes Development of Atherosclerosis.

Author information

1
From the Department of Biomedical Sciences (A.A., T.X.P., N.J., C.C., M.M., C.H.N., L.B.N.) and Department of Clinical Medicine (L.B.N.), University of Copenhagen, Denmark; and Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Denmark (C.C., E.D.B., L.B.N.).
2
From the Department of Biomedical Sciences (A.A., T.X.P., N.J., C.C., M.M., C.H.N., L.B.N.) and Department of Clinical Medicine (L.B.N.), University of Copenhagen, Denmark; and Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Denmark (C.C., E.D.B., L.B.N.). lars.bo.nielsen@regionh.dk.

Abstract

OBJECTIVE:

Atherosclerotic lesions contain hypoxic areas, but the pathophysiological importance of hypoxia is unknown. Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor in cellular responses to hypoxia. We investigated the hypothesis that HIF-1α 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-1α-expressing macrophages in murine atherosclerotic lesions. To investigate the significance of macrophage HIF-1α, Ldlr(-/-) mice were transplanted with bone marrow from mice with HIF-1α deficiency in the myeloid cells or control bone marrow. The HIF-1α deficiency in myeloid cells reduced atherosclerosis in aorta of the Ldlr(-/-) recipient mice by ≈72% (P=0.006).In vitro, HIF-1α-deficient macrophages displayed decreased differentiation to proinflammatory M1 macrophages and reduced expression of inflammatory genes. HIF-1α deficiency also affected glucose uptake, apoptosis, and migratory abilities of the macrophages.

CONCLUSIONS:

HIF-1α expression in macrophages affects their intrinsic inflammatory profile and promotes development of atherosclerosis.

KEYWORDS:

apoptosis; atherosclerosis; hypoxia; hypoxia-inducible factor 1α; macrophage

PMID:
27444197
DOI:
10.1161/ATVBAHA.116.307830
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center