Article

Detection of Osteopontin in Calcified Human Aortic Valves

Department of Medicine, Indiana University Medical Center, Indianapolis, USA.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 5.53). 04/1997; 17(3):547-52. DOI: 10.1161/01.ATV.17.3.547
Source: PubMed

ABSTRACT Cardiac valve calcification often results in obstruction of blood flow, which eventually leads to valve replacement. The molecular mechanisms resulting in valve calcification are unknown. Collagen and specific bone matrix proteins are thought to provide the framework for ectopic tissue calcification. This investigation was performed to determine whether the bone matrix protein osteopontin was present in calcified human aortic valves. Proteins extracted from human aortic valve tissue were subjected to polyacrylamide gel electrophoresis followed by Western blotting, using polyclonal antibodies directed against osteopontin. Fresh frozen tissue sections were also screened for osteopontin and macrophages using immunohistochemical techniques. Osteopontin was present in both heavily and minimally calcified aortic valves and absent in noncalcified purely regurgitant or normal aortic valves by both radioimmunoassay (n = 16) and immunohistochemical techniques (n = 8). Osteopontin colocalized with valvular calcific deposits, and macrophages were identified in the vicinity of osteopontin. These results, in addition to showing that osteopontin is present in calcified human aortic valves, suggest that osteopontin is a regulatory protein in pathological calcification. Identification of the cells producing osteopontin in abnormal cardiac valves and of proximate stimuli for its secretion may lead to novel therapeutic strategies to prevent and/or reverse calcific valve disease.

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    • "In vitro studies of cultured explants of stenotic valves have identified cells with osteoblastic characteristics that undergo phenotypic differentiation and spontaneous calcification [20]. These osteogenic cells express and produce a variety of regulatory bone matrix proteins including osteopontin (OPN) [21] [22] and bone morphogenetic proteins (BMPs) [17]. The initiation of mineralization (nucleation) may be stimulated by the presence of oxLDL [12] [17] or by the presence of cellular degradation products following apoptosis [8]. "
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    ABSTRACT: Calcific aortic valve disease (CAVD) represents a slowly progressive pathologic process associated with major morbidity and mortality. The process is characterized by multiple steps: inflammation, fibrosis, and calcification. Numerous studies focalized on its physiopathology highlighting different “actors” for the multiple “acts.” This paper focuses on the role of the tumor necrosis factor superfamily (TNFSF) members in the pathogenesis of CAVD. In particular, we discuss the clinical and experimental studies providing evidence of the involvement of tumor necrosis factor-alpha (TNF- α ), receptor activator of nuclear factor-kappa B (NF- κ B) ligand (RANKL), its membrane receptor RANK and its decoy receptor osteoprotegerin (OPG), and TNF-related apoptosis-inducing ligand (TRAIL) in valvular calcification.
    The Scientific World Journal 11/2013; 2013(5):875363. DOI:10.1155/2013/875363 · 1.73 Impact Factor
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    • "In vitro studies of cultured explants of stenotic valves have identified cells with osteoblastic characteristics that undergo phenotypic differentiation and spontaneous calcification [20]. These osteogenic cells express and produce a variety of regulatory bone matrix proteins including osteopontin (OPN) [21] [22] and bone morphogenetic proteins (BMPs) [17]. The initiation of mineralization (nucleation) may be stimulated by the presence of oxLDL [12] [17] or by the presence of cellular degradation products following apoptosis [8]. "
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    • "In vitro studies of cultured explants of stenotic valves have identified cells with osteoblastic characteristics that undergo phenotypic differentiation and spontaneous calcification [20]. These osteogenic cells express and produce a variety of regulatory bone matrix proteins including osteopontin (OPN) [21] [22] and bone morphogenetic proteins (BMPs) [17]. The initiation of mineralization (nucleation) may be stimulated by the presence of oxLDL [12] [17] or by the presence of cellular degradation products following apoptosis [8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Calcific aortic valve disease (CAVD) represents a slowly progressive pathologic process associated with major morbidity and mortality. The process is characterized by multiple steps: inflammation, fibrosis, and calcification. Numerous studies focalized on its physiopathology highlighting different "actors" for the multiple "acts. " This paper focuses on the role of the tumor necrosis factor superfamily (TNFSF) members in the pathogenesis of CAVD. In particular, we discuss the clinical and experimental studies providing evidence of the involvement of tumor necrosis factor-alpha (TNF-íµí»¼), receptor activator of nuclear factor-kappa B (NF-íµí¼…B) ligand (RANKL), its membrane receptor RANK and its decoy receptor osteoprotegerin (OPG), and TNF-related apoptosis-inducing ligand (TRAIL) in valvular calcification.
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