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(Circulation. 2007;115:2464-2467.)
© 2007 American Heart Association, Inc.

Editorial

Fetuin-A, Valve Calcification, and Diabetes

What Do We Understand?

Allen P. Burke, MD; Frank D. Kolodgie, PhD; Renu Virmani, MD

From the CVPath Institute, Gaithersburg, Md.

Correspondence to Dr Renu Virmani, CVPath Institute, 19 Firstfield Rd, Gaithersburg, MD 20878. E-mail rvirmani@cvpath.org

Key Words: Editorials • calcium • valves

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In the current issue of Circulation, Ix et al demonstrate an inverse correlation between mitral and aortic valve calcification and serum fetuin-A levels in a cross-sectional study of 970 patients with coronary artery disease and without renal disease.¹ Increased serum fetuin was significantly associated with diabetes mellitus, hypertriglyceridemia, serum albumin, and body mass index, with a weaker association with serum C-reactive protein, low-density lipoprotein cholesterol, and serum calcium. The link between aortic stenosis and fetuin held only in those without diabetes.¹ The data highlight the complex interactions of fetuin with inflammation, insulin resistance, and tissue calcification. Furthermore, the results, though intriguing, underscore our lack of understanding of the cellular mechanisms of calcification in diverse pathological substrates, such as the degenerating aortic leaflet and mitral annulus.

Article p 2533

Fetuin is a member of the cystatin superfamily of cysteine protease inhibitors, originally discovered as the major component of fetal bovine serum. It is a carrier for growth factors, binds to and inactivates transforming growth factor (TGF)–ß and bone morphogenic protein, and is a major component of mineralized bone.² Fetuin-A is also an acute-phase glycoprotein, produced in adults primarily in the liver, and is a powerful circulating inhibitor of hydroxyapatite formation. Mice that lack fetuin-A exhibit extensive soft-tissue calcification, which is accelerated on a mineral-rich diet, which suggests that fetuin-A acts to inhibit calcification systemically.³

In addition to its effects on mineralization, fetuin-A inhibits insulin receptor autophosphorylation and tyrosine kinase activity in vitro and in vivo. Fetuin-null knockout mice demonstrate improved . . . [Full Text of this Article]

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