Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated
in osteopontin-deficient mice
Authors Bruemmer D, Collins AR, Noh G, Wang W, Territo M, Arias-Magallona S, Fishbein
MC, Blaschke F, Kintscher U, Graf K, Law RE, Hsueh WA
Submitted By Submitted Externally on 6/7/2004
Status Published
Journal The Journal of clinical investigation
Year 2003
Date Published 11/1/2003
Volume : Pages 112 : 1318 - 1331
PubMed Reference 14597759
Abstract 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.


Investigators with authorship
NameInstitution
Willa HsuehOhio State University-Main Campus

Complications



Genes
SymbolDescription
Agtangiotensinogen
Angangiogenin
Cd68CD68 antigen
Mcpt1mast cell protease 1
Mmp2matrix metalloproteinase 2
Mmp9matrix metalloproteinase 9
Vcam1vascular cell adhesion molecule 1
2010317E24RikRIKEN cDNA 2010317E24 gene
Ccl2chemokine (C-C motif) ligand 2