Altered Vascular Remodeling in Osteopontin-Deficient Atherosclerotic Mice

Abstract

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.

18F-FDG PET Imaging of Murine Atherosclerosis: Association with Gene Expression of Key Molecular Markers

“…The expression of OPN has to our knowledge not previously been correlated with 18 F-FDG uptake. The high degree of correlation we found is supported by studies of knockout mice suggesting OPN as an important player in inflammation and atherogenesis [31], [32]. Both CD68 and OPN had independent predictive value for 18 F-FDG uptake in the multivariate linear regression analysis.…”

Npp1 promotes atherosclerosis in ApoE knockout mice

“…Matsui et al described 30–40% smaller atherosclerotic lesion areas in 36‐week‐old female Opn‐deficient atherosclerotic ( Opn/ApoE null) mice compared with ApoE null mice, due to less macrophages and lymphocytes in the lesion [37]. Also, in female 34‐week‐old Opn/ ApoE/ LDL receptor triple knockout mice, atherosclerotic lesion area is reduced compared with ApoE/ LDL receptor deficient mice [38]. Furthermore, it has been shown that transgenic mice that overexpress Opn are more prone to develop fatty streaks than wild‐type mice [39].…”

Transcription Profiles of Aortic Smooth Muscle Cells from Atherosclerosis-Prone and -Resistant Regions in Young Apolipoprotein E-Deficient Mice before Plaque Development

“…Osteopontin transgenic mice fed a high-cholesterol diet develop atherosclerotic lesions [59,60], whereas osteopontin deficiency reduces atherosclerosis in apoE–/– [61] and apoE/LDL receptor-deficient mice [62]. In vitro overexpression of osteopontin promotes vascular SMC proliferation [63], and in vivo overexpression is associated with increased thickening of the media with aging and of the intima after arterial injury [64].…”