Donate Help Contact The AHA Sign In Home
American Heart Association
Arteriosclerosis, Thrombosis, and Vascular Biology
Search: search_blue_button Advanced Search
Published Online
on January 30, 2003

Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print January 30, 2003, doi: 10.1161/01.ATV.0000058431.78833.F5
A more recent version of this article appeared on March 1, 2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
23/3/447    most recent
01.ATV.0000058431.78833.F5v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guo, J.
Right arrow Articles by Van Berkel, T. J.C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guo, J.
Right arrow Articles by Van Berkel, T. J.C.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Bone Marrow Transplantation
Hazardous Substances DB
*CHOLESTEROL
Related Collections
Right arrow Animal models of human disease
Right arrow Gene regulation
Right arrow Genetically altered mice
Right arrow Genetics of cardiovascular disease
Right arrow Mechanism of atherosclerosis/growth factors

Submitted on December 26, 2002
Accepted on January 15, 2003

Transplantation of Monocyte CC-Chemokine Receptor 2-Deficient Bone Marrow Into ApoE3-Leiden Mice Inhibits Atherogenesis

Jian Guo *; Miranda Van Eck ; Jaap Twisk ; Nobuyo Maeda ; G. Martin Benson ; Pieter H.E. Groot ; and Theo J.C. Van Berkel

From the Division of Biopharmaceutics (J.G., M.V.E., J.T., T.J.C.V.B.), Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands; Department of Pathology and Laboratory Medicine (N.M.), University of North Carolina Medical School, Chapel Hill, NC; and Atherosclerosis Department (G.M.B., P.H.E.G.), GlaxoSmithKline Pharmaceuticals, Stevenage, UK.

* To whom correspondence should be addressed. E-mail: j.guo{at}chem.leidenuniv.nl.

Objective--To determine the role of leukocyte CC-chemokine receptor 2 (CCR2) in the early development of atherosclerosis

Methods and Results--Bone marrow cells harvested from CCR2 (-/-) and CCR2 (+/+) mice were transplanted into ApoE3-Leiden mice, a mouse strain susceptible for diet-induced atherosclerosis. Eight weeks after bone marrow transplantation, the diet of regular chow was switched to a high-cholesterol diet (1% cholesterol, 15% fat, 0.5% cholate) for another 8 weeks to induce atherosclerosis. No significant differences in serum cholesterol and triglyceride levels were observed between the CCR2 (+/+) -> ApoE3-Leiden and CCR2 (-/-) -> ApoE3-Leiden mice. However, the mean cross-sectional aortic root lesion area of CCR2 (-/-) -> ApoE3-Leiden mice was only 2.94±1.94x104 µm2 compared with 20.94±12.71x104 µm2, for CCR2 (+/+) -> ApoE3-Leiden mice. Thus, the absence of CCR2 on leukocytes induces an 86% reduction of aortic lesion area as compared with controls (n=10, P<0.01).

Conclusion--These results provide direct evidence that CCR2 expressed by leukocytes plays a critical role in the initiation of early atherosclerosis and that pharmacological intervention in CCR2 function represents an attractive target to inhibit atherogenesis.
Key words: atherosclerosis • chemokines • bone marrow transplantation • transgenic animals




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
A. D. Westmuckett and K. L. Moore
Lack of Tyrosylprotein Sulfotransferase Activity in Hematopoietic Cells Drastically Attenuates Atherosclerosis in Ldlr-/- Mice
Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1730 - 1736.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
F. K. Swirski, R. Weissleder, and M. J. Pittet
Heterogeneous In Vivo Behavior of Monocyte Subsets in Atherosclerosis
Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1424 - 1432.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
J. Barlic and P. M. Murphy
Chemokine regulation of atherosclerosis
J. Leukoc. Biol., August 1, 2007; 82(2): 226 - 236.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
A.P.J.J. Bijnens, E. Lutgens, T. Ayoubi, J. Kuiper, A.J. Horrevoets, and M.J.A.P. Daemen
Genome-Wide Expression Studies of Atherosclerosis: Critical Issues in Methodology, Analysis, Interpretation of Transcriptomics Data
Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1226 - 1235.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
R. Kraemer, P. J. Baker, K. C. Kent, Y. Ye, J. J. Han, R. Tejada, M. Silane, R. Upmacis, R. Deeb, Y. Chen, et al.
Decreased Neurotrophin TrkB Receptor Expression Reduces Lesion Size in the Apolipoprotein E-Null Mutant Mouse
Circulation, December 6, 2005; 112(23): 3644 - 3653.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
I. Bot, J. Guo, M. Van Eck, P. J. Van Santbrink, P. H. E. Groot, R. B. Hildebrand, J. Seppen, T. J. C. Van Berkel, and E. A. L. Biessen
Lentiviral shRNA silencing of murine bone marrow cell CCR2 leads to persistent knockdown of CCR2 function in vivo
Blood, August 15, 2005; 106(4): 1147 - 1153.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
E. Lutgens, B. Faber, K. Schapira, C. T.A. Evelo, R. van Haaften, S. Heeneman, K. B.J.M. Cleutjens, A. P. Bijnens, L. Beckers, J. G. Porter, et al.
Gene Profiling in Atherosclerosis Reveals a Key Role for Small Inducible Cytokines: Validation Using a Novel Monocyte Chemoattractant Protein Monoclonal Antibody
Circulation, June 28, 2005; 111(25): 3443 - 3452.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
J. Guo, V. de Waard, M. Van Eck, R. B. Hildebrand, E. J.A. van Wanrooij, J. Kuiper, N. Maeda, G. M. Benson, P. H.E. Groot, and T. J.C. Van Berkel
Repopulation of Apolipoprotein E Knockout Mice With CCR2-Deficient Bone Marrow Progenitor Cells Does Not Inhibit Ongoing Atherosclerotic Lesion Development
Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 1014 - 1019.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
A. Schober, A. Zernecke, E. A. Liehn, P. von Hundelshausen, S. Knarren, W. A. Kuziel, and C. Weber
Crucial Role of the CCL2/CCR2 Axis in Neointimal Hyperplasia After Arterial Injury in Hyperlipidemic Mice Involves Early Monocyte Recruitment and CCL2 Presentation on Platelets
Circ. Res., November 26, 2004; 95(11): 1125 - 1133.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
C. Weber, A. Schober, and A. Zernecke
Chemokines: Key Regulators of Mononuclear Cell Recruitment in Atherosclerotic Vascular Disease
Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 1997 - 2008.
[Abstract] [Full Text] [PDF]


ATVB Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2003 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.