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

Minako Ishibashi, Kensuke Egashira, Qingwei Zhao, Ken ichi Hiasa, Kisho Ohtani, Yoshiko Ihara, Israel F. Charo, Shinobu Kura, Teruhisa Tsuzuki, Akira Takeshita, Kenji Sunagawa

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)e174-178
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number11
Publication statusPublished - Nov 2004

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CCR2 Receptors
Apolipoproteins E
Angiotensin II
Aneurysm
Atherosclerosis
Bone Marrow Transplantation
Bone Marrow
Leukocytes
Monocytes
Inflammation
Chemokine CCL2
Abdominal Aortic Aneurysm
Cell Wall
Blood Vessels
Cytokines
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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Bone marrow-derived monocyte chemoattractant protein-1 receptor CCR2 is critical in angiotensin II-induced acceleration of atherosclerosis and aneurysm formation in hypercholesterolemic mice. / Ishibashi, Minako; Egashira, Kensuke; Zhao, Qingwei; Hiasa, Ken ichi; Ohtani, Kisho; Ihara, Yoshiko; Charo, Israel F.; Kura, Shinobu; Tsuzuki, Teruhisa; Takeshita, Akira; Sunagawa, Kenji.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 24, No. 11, 11.2004, p. e174-178.

Research output: Contribution to journalArticle

Ishibashi, Minako ; Egashira, Kensuke ; Zhao, Qingwei ; Hiasa, Ken ichi ; Ohtani, Kisho ; Ihara, Yoshiko ; Charo, Israel F. ; Kura, Shinobu ; Tsuzuki, Teruhisa ; Takeshita, Akira ; Sunagawa, Kenji. / Bone marrow-derived monocyte chemoattractant protein-1 receptor CCR2 is critical in angiotensin II-induced acceleration of atherosclerosis and aneurysm formation in hypercholesterolemic mice. In: Arteriosclerosis, thrombosis, and vascular biology. 2004 ; Vol. 24, No. 11. pp. e174-178.
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abstract = "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.",
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AU - Zhao, Qingwei

AU - Hiasa, Ken ichi

AU - Ohtani, Kisho

AU - Ihara, Yoshiko

AU - Charo, Israel F.

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