期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 29, 期 5, 页码 665-670出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.108.183319
关键词
atherosclerosis; cytokines; immune system; hypoxia-inducible factor-1; T lymphocytes
资金
- Israeli Science Foundation [JG 832/06]
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-1 alpha in ApoE knockout murine lymphocytes, on experimental atherosclerosis. Methods and Results-ApoE(-/-) mice were submitted to intravenous hydrodynamic injection of empty plasmid or HIF-1 alpha P564A (HIF-1 alpha mutated stabilized construct). Robust expression of HIF-1 alpha 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-1 alpha-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-1 alpha injected mice. A reduced expression of IFN-gamma was evident in CD4+ spleen-derived lymphocytes and aortas of HIF-1 alpha-injected mice. Conclusions-HIF-1 alpha expression in mouse lymphocytes is associated with a reduced IFN-gamma expression and attenuation of experimental atherosclerosis. (Arterioscler Thromb Vasc Biol. 2009; 29: 665-670.)
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