title: Systemic and local levels of fetuin-A in calcific aortic valve stenosis.
abstract: Calcific aortic valve stenosis, the most frequent heart valve disorder in developed countries, is an actively regulated process with similarities to bone formation. Fetuin-A has recently been identified as a potent circulating inhibitor of calcification. While several studies involving patients with end-stage renal disease have shown an association between low serum fetuin-A and cardiovascular calcification, nothing is known about fetuin-A serum levels in non-renal patients with calcific aortic valve stenosis. Furthermore, while fetuin-A has been localized in calcified areas of atherosclerotic arteries, data about fetuin-A deposition in stenotic aortic valves are unavailable at present. Serum fetuin-A levels were determined in patients with (n=31) and without (n=28) calcified aortic valve stenosis by ELISA. Creatinine and CRP levels were determined and glomerular filtration rate (GFR) was calculated by the MDRD formula. Immunohistochemistry for fetuin-A was performed on human calcified stenotic (n=14) and control (n=8) aortic valves using a monoclonal antibody. Serum fetuin-A levels were lower in patients with calcific aortic stenosis as compared to the control group (1.41+/-0.33 versus 1.57+/-0,27 mg/dl; p=0.046). This difference was particularly evident in individuals with a normal GFR >or=60 ml/min (1.36+/-0.24 versus 1.63+/-0.27 mg/dl; p=0.007). Furthermore, specific staining of fetuin-A was found in stenotic valves but not in healthy control valves. The data suggest a role of fetuin-A in the pathogenesis calcific aortic valve stenosis independently of the renal function and support the concept that mechanisms of calcium homeostasis are involved in the development of calcific aortic stenosis.
authors.affiliation: First Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. jens.kaden@med.ma.uni-heidelberg.de
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Kaden
authors.forename: Jochen O
authors.initials: JO
authors.lastname: Reinöhl
authors.forename: Birgit
authors.initials: B
authors.lastname: Blesch
authors.forename: Martina
authors.initials: M
authors.lastname: Brueckmann
authors.forename: Dariusch
authors.initials: D
authors.lastname: Haghi
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
authors.forename: Fabian
authors.initials: F
authors.lastname: Schmitz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Klomfass
authors.forename: Manuela
authors.initials: M
authors.lastname: Pillich
authors.forename: Jan R
authors.initials: JR
authors.lastname: Ortlepp
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D002114:Calcinosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein