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PMID: 14597759 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice.

The Journal of clinical investigation ·Vol. 112 ·No. 9 ·2003-11-00 ·Pages 1318-31

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

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.

MeSH Terms
Angiotensin II/pharmacology Animals Aortic Aneurysm, Abdominal/etiology,therapy Apolipoproteins E/physiology Arteriosclerosis/etiology,therapy Cell Movement Cell Survival Chemokine CCL2/physiology Cytokines/biosynthesis Gene Expression Regulation/drug effects Leukocytes/physiology Macrophages/physiology Mice Mice, Inbred C57BL Osteopontin RNA, Messenger/analysis Receptors, CCR2 Receptors, Chemokine/physiology Sialoglycoproteins/genetics,physiology
Chemicals
Apolipoproteins E Ccr2 protein, mouse Chemokine CCL2 Cytokines RNA, Messenger Receptors, CCR2 Receptors, Chemokine Sialoglycoproteins Spp1 protein, mouse Osteopontin Angiotensin II
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Bruemmer Dennis
Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, Warren Hall, Suite 24-130, 900 Veteran Avenue, Los Angeles, California 90095, USA. [email protected]
Collins Alan R
Noh Grace
Wang Wei
Territo Mary
Arias-Magallona Sarah
Fishbein Michael C
Blaschke Florian
Kintscher Ulrich
Graf Kristof
Law Ronald E
Hsueh Willa A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI18141
Email
[email protected]
Published
2003-11-00
Pages
1318-31
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC228408
Subset
IM
Grants
NHLBI NIH HHS · U01 HL070526 · United States
NHLBI NIH HHS · HL-70526 · United States
External Links
PubMed source DOI: 10.1172/JCI18141 PMC Full Text View journal details
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