Clearance of fetuin-A–containing calciprotein particles is mediated by scavenger receptor-A
M Herrmann, C Schäfer, A Heiss, S Gräber… - Circulation …, 2012 - ahajournals.org
M Herrmann, C Schäfer, A Heiss, S Gräber, A Kinkeldey, A Büscher, MMN Schmitt…
Circulation research, 2012•ahajournals.orgRationale: 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 …
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 …
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.
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