title: Osteopontin upregulation in atherogenesis is associated with cellular oxidative stress triggered by the activation of scavenger receptors.
abstract: BACKGROUND
  Osteopontin (OPN) is a highly phosphorylated sialoprotein and a prominent component of mineralized extracellular matrices of bones and teeth. Although the structure of OPN has begun to be elucidated, the role of OPN overexpression in tissues distant from the bones and teeth remains poorly understood. In the present study, a rabbit model of hypercholesterolemia was employed to analyze the relationship between the vascular calcification process and OPN overexpression in the neointima of atherosclerotic plaques.
  
  
  METHODS
  OPN identification in the aorta of experimental animals fed with a high cholesterol diet was carried out by immunohistochemical procedures and Western blot analysis of tissue homogenates. Transmission electron microscopy was employed to localize target-like extracellular structures of atherosclerotic aortas. The human cell line T/G HA-VSMC was employed in the establishment of a ROS generation model employing the internalization of OxLDL particles.
  
  
  RESULTS
  Using immunohistochemical and Western blot analysis, OPN overexpression was detected in the aortas of rabbits fed a high-cholesterol diet. Results from the ultrastructural analysis of the rabbit neointima through transmission electron microscopy and from the detection of calcium phosphate precipitates by specific histochemical techniques, suggested that OPN may be functionally important as a regulator of vascular calcification. OPN was dramatically overexpressed by vascular smooth muscle cells in the presence of oxidized and acetylated LDL particles bound to scavenger receptors, thereby promoting cytosolic oxidative stress.
  
  
  CONCLUSIONS
  This study establishes the in vivo role of OPN in the intima of the aorta regulating calcium phosphate precipitate deposition in response to oxidative stress.
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, C.U. México, D.F., Mexico.
authors.forename: Azucena E
authors.initials: AE
authors.lastname: Jiménez-Corona
authors.forename: Salvador
authors.initials: S
authors.lastname: Damián-Zamacona
authors.forename: Armando
authors.initials: A
authors.lastname: Pérez-Torres
authors.forename: Abel
authors.initials: A
authors.lastname: Moreno
authors.forename: Jaime
authors.initials: J
authors.lastname: Mas-Oliva
mesh_terms: D000818:Animals; D050197:Atherosclerosis; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053495:Osteopontin / Q000378:metabolism*; D018384:Oxidative Stress; D011817:Rabbits; D051116:Receptors, Scavenger / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D051116:Receptors, Scavenger; D053495:Osteopontin