Clearance of fetuin-A--containing calciprotein particles is mediated by scavenger receptor-A

Circ Res. 2012 Aug 17;111(5):575-84. doi: 10.1161/CIRCRESAHA.111.261479. Epub 2012 Jul 2.


Rationale: Fetuin-A is a liver-derived plasma protein involved in the regulation of calcified matrix metabolism. Biochemical studies showed that fetuin-A is essential for the formation of protein-mineral complexes, called calciprotein particles (CPPs). CPPs must be cleared from circulation to prevent local deposition and pathological calcification.

Objective: We studied CPP clearance in mice and in cell culture to identify the tissues, cells, and receptors involved in the clearance.

Methods and results: In mice, fetuin-A-containing CPPs were rapidly cleared by the reticuloendothelial system, namely Kupffer cells of the liver and marginal zone macrophages of the spleen. Macrophages from scavenger receptor-AI/II (SR-A)-deficient mice cleared CPPs less efficiently than macrophages from wild-type mice, suggesting that SR-AI/II is involved in CPP binding and endocytosis. Accordingly, we found reduced clearance of CPPs in SR-A/MARCO-deficient mice.

Conclusions: We could demonstrate that fetuin-A-containing CPPs facilitate the clearance of mineral debris by macrophages via SR-A. Since the same receptor also contributes to the uptake of modified low-density lipoprotein particles in atherosclerosis, defective endocytosis of both types of particle may impinge on lipid as well as mineral debris clearance in calcifying atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Calcification, Physiologic / physiology
  • Calcinosis / metabolism
  • Calcinosis / pathology
  • Calcium / blood*
  • Calcium-Binding Proteins / metabolism
  • Carotid Arteries / cytology
  • Cattle
  • Cell Line
  • Endocytosis / physiology
  • Kupffer Cells / cytology
  • Kupffer Cells / metabolism*
  • Lipoproteins, LDL / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mononuclear Phagocyte System / metabolism
  • Phosphates / blood
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / metabolism
  • Spleen / cytology
  • alpha-2-HS-Glycoprotein / genetics
  • alpha-2-HS-Glycoprotein / metabolism*
  • alpha-2-HS-Glycoprotein / pharmacology


  • Ahsg protein, mouse
  • Apolipoproteins E
  • Calcium-Binding Proteins
  • Lipoproteins, LDL
  • Marco protein, mouse
  • Phosphates
  • Receptors, Immunologic
  • Scavenger Receptors, Class A
  • alpha-2-HS-Glycoprotein
  • Calcium