Systemic and local levels of fetuin-A in calcific aortic valve stenosis.
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.
Kaden
Jens J
JJ
First Department of Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. jens.kaden@med.ma.uni-heidelberg.de
Reinöhl
Jochen O
JO
Blesch
Birgit
B
Brueckmann
Martina
M
Haghi
Dariusch
D
Borggrefe
Martin
M
Schmitz
Fabian
F
Klomfass
Sebastian
S
Pillich
Manuela
M
Ortlepp
Jan R
JR
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
C556354:AHSG protein, human; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein