Hepcidin Destabilizes Atherosclerotic Plaque Via Overactivating Macrophages After Erythrophagocytosis
Hepcidin Destabilizes Atherosclerotic Plaque Via Overactivating Macrophages After Erythrophagocytosis
复制标题
铁调素通过吞噬红细胞后过度激活巨噬细胞来破坏动脉粥样硬化斑块的稳定
DOI：
10.1161/atvbaha.112.246108
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发表时间：
2012-05-01
影响因子：
8.7
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
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作者：
Li, Jing Jing;Meng, Xiao;Zhang, Yun
为了探讨血管hepcidin和动脉粥样硬化斑块stability.Methods和Results-Accelerated动脉粥样硬化病变之间的直接和因果关系，建立了载脂蛋白E缺陷（ApoE（-/-））小鼠血管周围的衣领放置。腺病毒过度表达hepcidin在颈动脉斑块形成过程中增强斑块内巨噬细胞浸润，抑制胶原蛋白和血管平滑肌细胞的含量，而hepcidin shRNA治疗发挥相反的作用。铁调素的过度表达或敲低不影响斑块脂质沉积，但增加或减少氧化低密度脂蛋白（ox-LDL）的水平内斑块巨噬细胞。在培养的巨噬细胞中，ox-LDL不仅增加活性氧的形成，炎症细胞因子的产生，和细胞凋亡，但也上调hepcidin的表达。然而，铁调素并没有夸大ox-LDL诱导的巨噬细胞的激活，直到红细胞吞噬作用的发作。而铁调素是关键的上调L-铁蛋白和H-铁蛋白在氧化低密度脂蛋白处理的红细胞吞噬巨噬细胞和动脉粥样硬化斑块，铁螯合剂的加入抑制细胞内脂质积累，活性氧形成，炎症细胞因子的表达，和细胞凋亡的红细胞吞噬macrophages.Conclusion-Hepcidin促进斑块不稳定，部分通过夸大炎症细胞因子的释放，细胞内脂质积累，氧化应激和巨噬细胞凋亡与铁潴留。（Arterioscler Thromb Vasc Biol.2012; 32：1158-1166.）
Objective-To explore a direct and causal relationship between vascular hepcidin and atherosclerotic plaque stability.Methods and Results-Accelerated atherosclerotic lesions were established by perivascular collar placement in apolipoprotein E-deficient (ApoE(-/-)) mice. Adenoviral overexpression of hepcidin in the carotid artery during plaque formation enhanced intraplaque macrophage infiltration and suppressed the contents of collagen and vascular smooth muscle cells, whereas hepcidin shRNA treatment exerts opposite effects. The overexpression or knockdown of hepcidin did not affect plaque lipid deposition but increased or decreased oxidized low-density lipoprotein (ox-LDL) levels within intraplaque macrophages. In cultured macrophages, ox-LDL not only increased reactive oxygen species formation, inflammatory cytokine production, and apoptosis but also upregulated hepcidin expression. However, hepcidin did not exaggerate the ox-LDL-induced activation of macrophages until an onset of erythrophagocytosis. Whereas hepcidin was critical for the upregulation of L-ferritin and H-ferritin in both ox-LDL-treated erythrophagocytosed macrophages and atherosclerotic plaques, the adding of iron chelators suppressed the intracellular lipid accumulation, reactive oxygen species formation, inflammatory cytokine expression, and apoptosis in erythrophagocytosed macrophages.Conclusion-Hepcidin promotes plaque destabilization partly by exaggerating inflammatory cytokine release, intracellular lipid accumulation, oxidative stress, and apoptosis in the macrophages with iron retention. (Arterioscler Thromb Vasc Biol. 2012; 32: 1158-1166.)