HIF-1α Overexpression and Experimental Murine Atherosclerosis
HIF-1α Overexpression and Experimental Murine Atherosclerosis
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DOI：
10.1161/atvbaha.108.183319
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发表时间：
2009-05-01
影响因子：
8.7
通讯作者：
George, Jacob
中科院分区：
文献类型：
--
作者：
Ben-Shoshan, Jeremy;Afek, Arnon;George, Jacob
背景：淋巴细胞在动脉粥样硬化的进展中起重要作用。最近，缺氧诱导因子-1 （HIF-1）被发现通过调节T细胞活化和细胞因子的产生来减轻炎症。我们研究了在ApoE敲除小鼠淋巴细胞中过表达HIF-1 α对实验性动脉粥样硬化的影响。方法与结果：将apoe（-/-）小鼠静脉注射空质粒或HIF-1 α P564A （HIF-1 α突变稳定构建体）。HIF-1 α在受体动物的脾脏细胞中有明显的表达。RT-PCR检测HIF-1 α处理小鼠脾细胞中IL-10表达升高，ifn - γ表达降低。注射后一周，抗体阵列分析显示与T辅助1向T辅助2转移的模式一致。在牺牲时，对注射HIF-1 α的小鼠主动脉窦病变的评估显示斑块大小显着减少。注射HIF-1小鼠的CD4+脾源淋巴细胞和主动脉中ifn - γ的表达明显降低。结论- hif -1 α在小鼠淋巴细胞中的表达与ifn - γ表达降低和实验性动脉粥样硬化的衰减有关。（中国生物医学杂志，2009;29:665-670）
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.)