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The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification
Open accessAbstract
Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein alpha2-Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level. Ahsg-deficient mice are phenotypically normal, but develop severe calcification of various organs on a mineral and vitamin D-rich diet and on a normal diet when the deficiency is combined with a DBA/2 genetic background. This phenotype is not associated with apparent changes in calcium and phosphate homeostasis, but with a decreased inhibitory activity of the Ahsg-deficient extracellular fluid on mineral formation. The same underlying principle may contribute to many calcifying disorders including calciphylaxis, a syndrome of severe systemic calcification in patients with chronic renal failure. Taken together, our data demonstrate a critical role of Ahsg as an inhibitor of unwanted mineralization and provide a novel therapeutic concept to prevent ectopic calcification accompanying various diseases.
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Citations
Cited by
Arterial Calcifications and Bone Histomorphometry in End-Stage Renal Disease
London, G. M., Marty, C., Marchais, S. J., Guerin, A. P., Metivier, F., & de Vernejoul, M.-C. (2004) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000129337.50739.48 · Cited by 594
Stenvinkel, P., Carrero, J. J. A. A., Axelsson, J., Lindholm, B., Heimbu[Combining Diaeresis]rger, O., & Massy, Z. (2008) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.03670807 · Cited by 561
Pathophysiology of Vascular Calcification in Chronic Kidney Disease
Moe, S. M., & Chen, N. X. (2004) · Circulation Research · doi:10.1161/01.res.0000141775.67189.98 · Cited by 502
The impact of insulin resistance on the kidney and vasculature
Artunc, F., Schleicher, E., Weigert, C., Fritsche, A., Stefan, N., & Häring, H.-U. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.145 · Cited by 462
Vascular Calcification—New Insights into Its Mechanism
Lee, S. J., Lee, I.-K., & Jeon, J.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082685 · Cited by 438
Metadata
- Authors
- Schäfer, C., Heiss, A., Schwarz, A., Westenfeld, R., Ketteler, M., Floege, J., Müller-Esterl, W., Schinke, T., & Jahnen-Dechent, W.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-08-01
- Volume
- 112
- Issue
- 3
- Pages
- 357-366
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2167455623
- Cited by
- 924
- References
- 0
- FWCI
- 22.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Schäfer, C., Heiss, A., Schwarz, A., Westenfeld, R., Ketteler, M., Floege, J., Müller-Esterl, W., Schinke, T., & Jahnen-Dechent, W. (2003). The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. Journal of Clinical Investigation. https://doi.org/10.1172/jci17202
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