Abstract | BACKGROUND: METHODS AND RESULTS: We created coils with a 50:50 poly-dl-lactic glycolic acid (PLGA) coating that released MCP-1 at 3 different doses (100 μg/mL, 1 mg/mL, and 10 mg/mL) and performed a dose-response study for effect on intra-aneurysmal tissue healing in a murine carotid aneurysm model. We then demonstrated that MCP-1 (100 μg/mL)-releasing coils promote significantly greater aneurysm tissue in-growth than bare platinum or PLGA-only coils. We show that MCP-1 recruits the migration of fibroblasts, macrophages, smooth muscle cells, and endothelial cells in vitro in cell migration assays and in vivo in murine carotid aneurysms. Using gfp(+) bone marrow-transplant chimeric mice, we demonstrate that the MCP-1-recruited fibroblasts and macrophages are derived from the bone marrow. We demonstrate that this MCP-1-mediated vascular inflammatory repair occurs via a macrophage inflammatory protein (MIP)-1α- and MIP-2-dependent pathway. MCP-1 released from coiled murine aneurysms causes significant upregulation of MIP-1α and MIP-2 expression by cytokine array assay. Blocking MIP-1α and MIP-2 with antagonist antibody causes a significant decrease in MCP-1-mediated intra-aneurysmal tissue healing. CONCLUSION: Our findings suggest that MCP-1 has a critical role in promoting inflammatory intra-aneurysmal tissue healing in an MIP-1α- and MIP-2-dependent pathway.
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Authors | Brian L Hoh, Koji Hosaka, Daniel P Downes, Kamil W Nowicki, Cristina E Fernandez, Christopher D Batich, Edward W Scott |
Journal | Circulation
(Circulation)
Vol. 124
Issue 20
Pg. 2243-52
(Nov 15 2011)
ISSN: 1524-4539 [Electronic] United States |
PMID | 22007074
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ccl2 protein, mouse
- Ccl3 protein, mouse
- Chemokine CCL2
- Chemokine CCL3
- Chemokine CXCL2
- Cxcl2 protein, mouse
- Inflammation Mediators
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Topics |
- Animals
- Carotid Artery, Internal, Dissection
(drug therapy, metabolism, pathology)
- Chemokine CCL2
(administration & dosage, metabolism)
- Chemokine CCL3
(physiology)
- Chemokine CXCL2
(physiology)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Female
- Inflammation Mediators
(physiology)
- Mice
- Mice, Inbred C57BL
- Signal Transduction
(physiology)
- Wound Healing
(physiology)
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