Angiotensin II–accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice
AUTOR(ES)
Bruemmer, Dennis
FONTE
American Society for Clinical Investigation
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=228408Documentos Relacionados
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