Bone marrow–derived monocyte chemoattractant protein-1 receptor CCR2 is critical in angiotensin II–induced acceleration of atherosclerosis and aneurysm formation …
M Ishibashi, K Egashira, Q Zhao, K Hiasa… - … , and vascular biology, 2004 - Am Heart Assoc
M Ishibashi, K Egashira, Q Zhao, K Hiasa, K Ohtani, Y Ihara, IF Charo, S Kura, T Tsuzuki…
Arteriosclerosis, thrombosis, and vascular biology, 2004•Am Heart AssocAngiotensin 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 …
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 …
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.
Conclusion— 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.
Am Heart Assoc