Clearance of Fetuin-A--Containing Calciprotein Particles is Mediated by Scavenger Receptor-A
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 wildtype 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: Here, 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.
- Received November 23, 2011.
- Accepted July 2, 2012.
- Copyright © 2012, American Heart Association