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Editorial
. 2019 Mar;39(3):303-305.
doi: 10.1161/ATVBAHA.119.312369.

Ironing-Out the Role of Hepcidin in Atherosclerosis

Liang Guo  1 , Atsushi Sakamoto  1 , Anne Cornelissen  1 , Charles C Hong  2 , Aloke V Finn  1   2
Affiliations
Editorial

Ironing-Out the Role of Hepcidin in Atherosclerosis

Liang Guo et al. Arterioscler Thromb Vasc Biol. 2019 Mar.
No abstract available

Keywords: Editorials; atherosclerosis; cardiovascular disease; coronary artery disease; homeostasis; inflammation.

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Figures

Figure 1
Figure 1. Effect of Hepcidin on Macrophages Phenotype and Function in the Setting of Atherosclerosis
(a): Hepcidin inhibits iron release from macrophage via down-regulation of iron transporter ferroportin (FPN) and enhance intra-cellular iron storage. Elevated intra-cellular iron accumulation results in incorporation increased oxidized low-density lipoprotein cholesterol (ox-LDL) retention via transporter such as CD36 and LDL recepter-1 (LOX-1), and increased inflammatory signaling (LPS) via toll-like recepter-4 (TLR4), decreasing cholesterol efflux, and intra-cellular reactive oxygen species (ROS) generation. Overall these cells exhibit a phenotype consistent with pro-inflammatory foamy macrophage phenotype. In this condition, macrophages contribute to atherosclerosis progression (b). (c): In the low/no hepcidin environment, intra-cellular iron is actively exported out of the macrophage via FPN. Lowering intracellular iron within the macrophage suppresses LDL uptake and increases its export via ABC transporters, lowers TLR4-dependent inflammatory signaling and ROS production. These effects are thought to be anti-atherogenic (d). At the same time low iron level enhance hypoxia inducible factor-1 alpha (HIF-1α) nuclear translocation, promoting vascular endothelial target gene expression, endothelial permeability, and inflammatory signaling. The latter effect may be pro-atherogenic especially in the setting of intraplaque hemorrhage. Abbreviations: ABCA1, ATP-binding cassette sub-family A member 1; CD, cluster differentiation; Fe, iron; FPN, ferroportin; HIF1α, Hypoxia inducible factor-1 alpha; HDL, high-density lipoprotein; LOX-1, low-density lipoprotein recepter-1; LPS, lipopolysaccharide; NC, necrotic core; ox-LDL, oxidized low-density lipoprotein cholesterol; ROS, reactive oxygen species; TLR4, tall-like receptor; TNF-α, tumor necrosis factor-alpha; VEGF-α, vascular endothelial grows factor-alpha.
See this image and copyright information in PMC

Comment on

  • Hepcidin Deficiency Protects Against Atherosclerosis.
    Malhotra R, Wunderer F, Barnes HJ, Bagchi A, Buswell MD, O'Rourke CD, Slocum CL, Ledsky CD, Peneyra KM, Sigurslid H, Corman B, Johansson KB, Rhee DK, Bloch KD, Bloch DB. Malhotra R, et al. Arterioscler Thromb Vasc Biol. 2019 Feb;39(2):178-187. doi: 10.1161/ATVBAHA.118.312215. Arterioscler Thromb Vasc Biol. 2019. PMID: 30587002 Free PMC article.

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