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Arterioscler Thromb Vasc Biol. 2009 May;29(5):665-70. doi: 10.1161/ATVBAHA.108.183319. Epub 2009 Feb 26.

HIF-1alpha overexpression and experimental murine atherosclerosis.

Author information

1
Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Abstract

BACKGROUND:

Lymphocytes play an important role in the progression of atherosclerosis. Recently, hypoxia inducible factor-1 (HIF-1) was found to attenuate inflammation by regulating T cell activation and cytokine production. We studied the effects of overexpression of HIF-1alpha in ApoE knockout murine lymphocytes, on experimental atherosclerosis.

METHODS AND RESULTS:

ApoE-/- mice were submitted to intravenous hydrodynamic injection of empty plasmid or HIF-1alphaP564A (HIF-1alpha mutated stabilized construct). Robust expression of HIF-1alpha was evident in spleen cells of recipient animals. Increased expression of IL-10 as well as decreased expression of IFN-gamma was measured in splenocytes of HIF-1alpha-treated mice by RT-PCR. One week postinjection, antibody array analysis revealed a pattern consistent with a T helper 1 to T helper 2 shift. On sacrifice, assessment of aortic sinus lesions revealed a significant reduction in plaque size in HIF-1alpha injected mice. A reduced expression of IFN-gamma was evident in CD4+ spleen-derived lymphocytes and aortas of HIF-1alpha-injected mice.

CONCLUSIONS:

HIF-1alpha expression in mouse lymphocytes is associated with a reduced IFN-gamma expression and attenuation of experimental atherosclerosis.

PMID:
19251587
DOI:
10.1161/ATVBAHA.108.183319
[Indexed for MEDLINE]
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