[HTML][HTML] Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice

D Bruemmer, AR Collins, G Noh… - The Journal of …, 2003 - Am Soc Clin Investig
D Bruemmer, AR Collins, G Noh, W Wang, M Territo, S Arias-Magallona, MC Fishbein…
The Journal of clinical investigation, 2003Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation