Altered vascular remodeling in osteopontin-deficient atherosclerotic mice.
BACKGROUND
Osteopontin (OPN) is a cell-binding phosphoprotein with proposed functions in atherosclerosis. The aim of this study was to examine how OPN deficiency affects the atherosclerotic process.


METHODS
ApoE/LDL receptor/OPN triple knockout (ALO) mice were generated by crossing OPN null mice with ApoE/LDL receptor-deficient (AL) mice. Analysis were made on tissue sections from the aortic arch of 8-, 20- and 34-week female AL and ALO mice and included morphometric measurements, collagen staining, TUNEL staining and immunohistochemistry with antibodies to OPN, macrophages and proliferating cellular nuclear antigen (PCNA).


RESULTS
Lesion and media areas were significantly smaller and collagen accumulation in lesions was significantly reduced in 34-week-old ALO mice compared with AL mice. The numbers of proliferating and apoptotic cells were increased in lesions of 34 weeks old ALO mice. Furthermore, the plasma levels of SAA and total cholesterol were significantly decreased in 34 weeks old ALO mice.


CONCLUSIONS
The present study shows that OPN deficiency reduces atherogenesis in atherosclerotic mice. The results corroborate and extend recently published findings and also include novel data on the role of OPN in the process of remodeling, inflammation and lipid metabolism.
Ström
Asa
A
Department of Cell and Molecular Biology, Section for Connective Tissue Biology, Lund University, Lund, Sweden.
Franzén
Ahnders
A
Wängnerud
Christel
C
Knutsson
Ann-Katrin
AK
Heinegård
Dick
D
Hultgårdh-Nilsson
Anna
A
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001053:Apolipoproteins / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency; D017209:Apoptosis; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D053495:Osteopontin; D011973:Receptors, LDL / Q000172:deficiency; D000685:Serum Amyloid A Protein / Q000378:metabolism; D012795:Sialoglycoproteins / Q000172:deficiency*
D001053:Apolipoproteins; D001057:Apolipoproteins E; D011973:Receptors, LDL; D000685:Serum Amyloid A Protein; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D003094:Collagen; D002784:Cholesterol