HIF-1alpha overexpression and experimental murine atherosclerosis.
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.


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.
Ben-Shoshan
Jeremy
J
Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Afek
Arnon
A
Maysel-Auslender
Sofia
S
Barzelay
Aya
A
Rubinstein
Ardon
A
Keren
Gad
G
George
Jacob
J
D000818:Animals; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D051379:Mice; D013154:Spleen / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007371:Interferon-gamma