title: Osteopontin is expressed in human aortic valvular lesions.
abstract: BACKGROUND
  Nonrheumatic stenosis of trileaflet aortic valves, in which calcification is a prominent feature, has been termed a "degenerative" condition, but it has been demonstrated recently that chronic inflammation is a characteristic feature of the developing lesion of aortic stenosis. This observation raised the possibility that calcification in the aortic valve might be actively regulated. Thus, the present study investigated whether osteopontin, a protein implicated in the regulation of both normal and dystrophic calcification, could be detected in lesions of valvular aortic stenosis.
  
  
  RESULTS
  Morphological and immunohistochemical studies were performed on 14 human aortic valves, representing a range of pathology from normal to clinically stenotic. The extent of calcification and macrophage accumulation and their relation to the presence of osteopontin protein were characterized. Highly statistically significant associations were found between the degree of osteopontin expression and the degrees of both calcification and macrophage accumulation in early through late lesions of aortic stenosis. Further, in situ hybridization localized osteopontin mRNA to a subset of lesion macrophages.
  
  
  CONCLUSIONS
  These results suggest that, rather than representing a degenerative and unmodifiable process, calcification in aortic stenosis may be, in part, an actively regulated process with the potential for control either through modification of inflammation or synthesis of proteins such as osteopontin, which may modulate calcification in this tissue.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: O'Brien
authors.forename: J
authors.initials: J
authors.lastname: Kuusisto
authors.forename: D D
authors.initials: DD
authors.lastname: Reichenbach
authors.forename: M
authors.initials: M
authors.lastname: Ferguson
authors.forename: C
authors.initials: C
authors.lastname: Giachelli
authors.forename: C E
authors.initials: CE
authors.lastname: Alpers
authors.forename: C M
authors.initials: CM
authors.lastname: Otto
mesh_terms: D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000378:metabolism* / Q000473:pathology; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D010750:Phosphoproteins; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin