Effect of Copper on Hemostasis and the Inflammatory Response

Effect of Copper on Hemostasis and the Inflammatory Response

PDGF plays a significant role not only during hemostasis but also during the several stages of wound repair. It stimulates not only the proliferation and migration of fibroblasts and smooth muscle cells but also the migration of inflammatory cells such as neutrophils and macrophages. In vitro studies have provided insight that the cell migration stimulated by PDGF is copper dependent and that copper plays an important role in the first two stages of wound healing. Copper accumulates during the inflammation phase, where it will be used by inflammatory cells such as macrophages.

Effect of Copper on Proliferation

Copper's role in facilitating angiogenesis has been known for some time, but only more recent studies have shed light on the specific copper targets. VEGF is an important growth factor which stimulates angiogenesis, a key part of the proliferation phase. Copper is able to induce VEGF expression in keratinocytes, which is confirmed by enhanced VEGF expression in copper-treated wounds. Furthermore, the release of two polypeptides also involved in angiogenesis, fibroblast growth factor 1 (FGF-1) and interleukin 1α (IL-1α), is upregulated by copper.

Effect of Copper on Remodeling

During remodeling, fibronectin mats are formed to strengthen the scar. Fibronectin stabilization and cell ingrowth are stimulated by low concentrations of copper. Copper also forms complexes with the tripeptide glycyl-l-histidyl-l-lysine (GHK), which upregulate important remodeling proteins such as collagen, elastin, metalloproteinases, VEGF, fibroblast growth factor, and nerve growth factor. Furthermore, cross-linking of collagen and elastin is catalyzed by the copper-dependent enzyme lysyl oxidase (LOX).

（To be continued）

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