Bone marrow-derived monocyte chemoattractant protein-1 receptor CCR2 is critical in angiotensin II-induced acceleration of atherosclerosis and aneurysm formation in hypercholesterolemic mice.

Abstract

UNLABELLED:

Angiotensin II (Ang II) is implicated in atherogenesis by activating inflammatory responses in arterial wall cells. Ang II accelerates the atherosclerotic process in hyperlipidemic apoE-/- mice by recruiting and activating monocytes. Monocyte chemoattractant protein-1 (MCP-1) controls monocyte-mediated inflammation through its receptor, CCR2. The roles of leukocyte-derived CCR2 in the Ang II-induced acceleration of the atherosclerotic process, however, are not known. We hypothesized that deficiency of leukocyte-derived CCR2 suppresses Ang II-induced atherosclerosis.

METHODS AND RESULTS:

A bone marrow transplantation technique (BMT) was used to develop apoE-/- mice with and without deficiency of CCR2 in leukocytes (BMT-apoE-/-CCR2+/+ and BMT-apoE-/-CCR2-/- mice). Compared with BMT-apoE-/-CCR2+/+ mice, Ang II-induced increases in atherosclerosis plaque size and abdominal aortic aneurysm formation were suppressed in BMT-apoE-/-CCR2-/- mice. This suppression was associated with a marked decrease in monocyte-mediated inflammation and inflammatory cytokine expression.

CONCLUSIONS:

Leukocyte-derived CCR2 is critical in Ang II-induced atherosclerosis and abdominal aneurysm formation. The present data suggest that vascular inflammation mediated by CCR2 in leukocytes is a reasonable target of therapy for treatment of atherosclerosis.

• Authors: Minako Ishibashi, Kensuke Egashira, Qingwei Zhao, Ken-ichi Hiasa, Kisho Ohtani, Yoshiko Ihara, Israel F Charo, Shinobu Kura, Teruhisa Tsuzuki, Akira Takeshita, Kenji Sunagawa
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 24 Issue 11 Pg. e174-8 (Nov 2004) ISSN: 1524-4636 [Electronic] United States
• PMID: 15331433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Ccr2 protein, mouse
• Receptors, CCR2
• Receptors, Chemokine
• Angiotensin II

Topics

• Angiotensin II (metabolism)
• Animals
• Aortic Aneurysm, Abdominal (etiology)
• Apolipoproteins E (deficiency)
• Arteriosclerosis (pathology)
• Bone Marrow (chemistry)
• Bone Marrow Transplantation (methods)
• Leukocytes (chemistry, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred Strains
• Monocytes (chemistry, metabolism)
• Receptors, CCR2
• Receptors, Chemokine (deficiency, physiology)