| First Author | Bruemmer D | Year | 2003 |
| Journal | J Clin Invest | Volume | 112 |
| Issue | 9 | Pages | 1318-31 |
| PubMed ID | 14597759 | Mgi Jnum | J:86531 |
| Mgi Id | MGI:2680730 | Doi | 10.1172/JCI18141 |
| Citation | Bruemmer D, et al. (2003) Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. J Clin Invest 112(9):1318-31 |
| abstractText | Osteopontin (OPN) is expressed in atherosclerotic lesions, particularly in diabetic patients. To determine the role of OPN in atherogenesis, ApoE-/-OPN+/+, ApoE-/-OPN+/-, and ApoE-/-OPN-/- mice were infused with Ang II, inducing vascular OPN expression and accelerating atherosclerosis. Compared with ApoE-/-OPN+/+ mice, ApoE-/-OPN+/- and ApoE-/-OPN-/- mice developed less Ang II-accelerated atherosclerosis. ApoE-/- mice transplanted with bone marrow derived from ApoE-/-OPN-/- mice had less Ang II-induced atherosclerosis compared with animals receiving ApoE-/-OPN+/+ cells. Aortae from Ang II-infused ApoE-/-OPN-/- mice expressed less CD68, C-C-chemokine receptor 2, and VCAM-1. In response to intraperitoneal thioglycollate, recruitment of leukocytes in OPN-/- mice was impaired, and OPN-/- leukocytes exhibited decreased basal and MCP-1-directed migration. Furthermore, macrophage viability in atherosclerotic lesions from Ang II-infused ApoE-/-OPN-/- mice was decreased. Finally, Ang II-induced abdominal aortic aneurysm formation in ApoE-/-OPN-/- mice was reduced and associated with decreased MMP-2 and MMP-9 activity. These data suggest an important role for leukocyte-derived OPN in mediating Ang II-accelerated atherosclerosis and aneurysm formation. |
