Hypoxia-Inducible Factor-1α Expression in Macrophages Promotes Development of Atherosclerosis.
Arterioscler Thromb Vasc Biol
; 36(9): 1782-90, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27444197
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 ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aorta Torácica
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Doenças da Aorta
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Aterosclerose
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Subunidade alfa do Fator 1 Induzível por Hipóxia
/
Células Espumosas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article