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Arterioscler Thromb Vasc Biol. 2012 May;32(5):1158-66. doi: 10.1161/ATVBAHA.112.246108. Epub 2012 Mar 1.

Hepcidin destabilizes atherosclerotic plaque via overactivating macrophages after erythrophagocytosis.

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Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Shandong University, Jinan, Shandong, China.

Erratum in

  • Arterioscler Thromb Vasc Biol. 2012 Jul;32(7):e50.



To explore a direct and causal relationship between vascular hepcidin and atherosclerotic plaque stability.


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.


Hepcidin promotes plaque destabilization partly by exaggerating inflammatory cytokine release, intracellular lipid accumulation, oxidative stress, and apoptosis in the macrophages with iron retention.

[Indexed for MEDLINE]

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