title: Circulating soluble receptor for advanced glycation end-product levels are decreased in patients with calcific aortic valve stenosis.
abstract: OBJECTIVE
  It has been suggested that atherosclerotic mechanisms are involved in the pathogenesis of aortic valve stenosis (AVS). We hypothesised that low levels of the soluble receptor for advanced glycation end-products (sRAGE) might be associated with AVS due to its clinical and pathological associations with atherosclerosis.
  
  
  METHODS
  We enrolled 75 consecutive patients with severe AVS scheduled for surgical aortic valve replacement and 39 controls without AVS matched for age and gender. Besides the traditional risk factors, we evaluated plasma levels of sRAGE, C-reactive protein (CRP) and IL-6. All patients underwent transthoracic echocardiography, carotid arteries ultrasound scan and coronary angiography. The aortic and coronary calcium by multislice computed tomography was assessed in AVS patients.
  
  
  RESULTS
  The values of sRAGE were significantly lower (p<0.01) in AVS patients than in controls, while the CRP levels were significantly higher (p<0.05) in AVS patients than in controls. In AVS patients the sRAGE levels correlated inversely with age, cholesterol levels and coronary calcification. In all study subjects, we found an inverse correlation between circulating sRAGE and the number of echographically assessed sites of calcification (ANOVA, p<0.0001). In multivariable logistic regression analysis after adjustment for potential confounders, the sRAGE levels were significantly and independently associated with the risk of AVS (OR=0.997, 95% CI=0.994-1.000, p=0.048).
  
  
  CONCLUSIONS
  Since sRAGE could exert antiatherogenic effects by preventing inflammatory responses mediated by cell surface RAGE activation, low levels in AVS patients indicate that ligand-RAGE axis could contribute to pathogenesis of AVS.
authors.affiliation: CNR, Institute of Clinical Physiology, Pisa, Italy. lapina@ifc.cnr.it
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Basta
authors.forename: Anca I
authors.initials: AI
authors.lastname: Corciu
authors.forename: Annamaria
authors.initials: A
authors.lastname: Vianello
authors.forename: Serena
authors.initials: S
authors.lastname: Del Turco
authors.forename: Ilenia
authors.initials: I
authors.lastname: Foffa
authors.forename: Teresa
authors.initials: T
authors.lastname: Navarra
authors.forename: Dante
authors.initials: D
authors.lastname: Chiappino
authors.forename: Sergio
authors.initials: S
authors.lastname: Berti
authors.forename: Annamaria
authors.initials: A
authors.lastname: Mazzone
mesh_terms: D000368:Aged; D001021:Aortic Valve / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000097:blood* / Q000601:surgery; D002097:C-Reactive Protein / Q000096:biosynthesis; D002114:Calcinosis / Q000097:blood*; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D017023:Coronary Angiography / Q000379:methods; D004452:Echocardiography / Q000379:methods; D005260:Female; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D002097:C-Reactive Protein