Background: The aim of this study was to analyze the arterial wall response to plaque-prone hemodynamic environments, known to occur mainly in areas of arterial trees such as bifurcations and branching points. In these areas, the vasculature is exposed to cyclically reversing flow that induces an endothelial dysfunction predisposing thus arteries to local development of atherosclerotic plaques. Methods: We used an ex vivo perfusion system that allows culturing arterial segments under different hemodynamic conditions. Porcine carotid arteries were exposed for 3 days to unidirectional high and low shear stress (6 ± 3 and 0.3 ± 0.1 dyn/cm²) as well as to oscillatory shear stress (0.3 ± 3 dyn/cm²). This latter condition mimics the hemodynamics present at plaque-prone areas. At the end of the perfusion, the influence of different flow patterns on arterial metabolism was assessed in terms of matrix turnover as well as of smooth muscle cell function, differentiation and migration. Results: Our results show that after 3 days of perfusion none of the applied conditions influence smooth muscle cell phenotype retaining their full contraction capacity. However, an increase in the expression level of matrix metalloproteinase-2 and -9, as well as a decrease in plasminogen activator inhibitor-1 expression were observed in arteries exposed to oscillatory shear stress when compared to arteries exposed to unidirectional shear stress. Conclusion: These observations suggest that plaque-prone hemodynamic environment triggers a vascular wall remodelling process and promotes changes in arterial wall metabolism, with important implication in atherogenesis.

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Hepcidin, which has been recently identified both by biochemical and genomic approaches, is a 25 amino acid polypeptide synthesized mainly by hepatocytes and secreted into the plasma. Besides its potential activity in antimicrobial defense, hepcidin plays a major role in iron metabolism. It controls two key steps of iron bioavailability, likely through a hormonal action: digestive iron absorption by enterocytes and iron recycling by macrophages. In humans, this could explain that low levels of hepcidin found during juvenile haemochromatosis and HFE-1 genetic haemochromatosis are associated with an iron overload phenotype. Conversely, an increase of hepcidin expression is suspected to play a major role in the development of anemia of chronic inflammatory diseases. However, the regulatory mechanisms of hepcidin expression are multiple, including iron-related parameters, anemia, hypoxia, inflammation and hepatocyte function. Therefore, many physiological and pathological situations may modulate hepcidin expression and subsequently iron metabolism. A better knowledge of the biological effects of hepcidin and of its expression regulatory mechanisms will clarify the place of hepcidin in the diagnosis and treatment of iron-related diseases.

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