Figure 1.

Graphical representation of main physiological roles of hepatic-secreted Fetuin-A. Under physiological conditions, Fetuin-A (Fet-A) enhances the absorption and fixation of essential minerals, calcium, and phosphate in the form of hydroxyapatite substituted with a carbonate. Moreover, Fet-A acts as a carrier of insoluble phosphate and calcium, and forms stable mineral complexes, more soluble in the bloodstream, preventing the precipitation of calcium salts through the mediation of their clearance, and the consequent occurrence of vascular calcifications. Fet-A functions as a negative regulator of the innate immune response by inhibiting Lipopolysaccharide (LPS)- or Interferon (IFN)-γ-induced High mobility group box 1 protein (HMGB1) release in macrophages in response to lethal endotoxemia or sepsis.