| First Author | Fu C | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 10 | Pages | 2418-26 |
| PubMed ID | 22904274 | Mgi Jnum | J:201475 |
| Mgi Id | MGI:5514195 | Doi | 10.1161/ATVBAHA.112.255786 |
| Citation | Fu C, et al. (2012) Monocyte chemoattractant protein-1/CCR2 axis promotes vein graft neointimal hyperplasia through its signaling in graft-extrinsic cell populations. Arterioscler Thromb Vasc Biol 32(10):2418-26 |
| abstractText | OBJECTIVE: To evaluate direct versus indirect monocyte chemoattractant protein (MCP)-1/CCR2 signaling and to identify the cellular producers and effectors for MCP-1 during neointimal hyperplasia (NIH) development in vein grafts. METHODS AND RESULTS: Genomic analysis revealed an overrepresentation of 13 inflammatory pathways in wild-type vein grafts compared with CCR2 knockout vein grafts. Further investigation with various vein graft-host combinations of MCP-1- and CCR2-deficient mice was used to modify the genotype of cells both inside (graft-intrinsic group) and outside (graft-extrinsic group) the vein wall. CCR2 deficiency inhibited NIH only when present in cells extrinsic to the graft wall, and MCP-1 deficiency required its effectiveness in cells both intrinsic and extrinsic to the graft wall to suppress NIH. Deletion of either MCP-1 or CCR2 was equally effective in inhibiting NIH. CCR2 deficiency in the predominant neointimal cell population had no impact on NIH. Direct MCP-1 stimulation of primary neointimal smooth muscle cells had minimal influence on cell proliferation and matrix turnover, confirming an indirect mechanism of action. CONCLUSIONS: MCP-1/CCR2 axis accelerates NIH via its signaling in graft-extrinsic cells, particularly circulating inflammatory cells, with cells both intrinsic and extrinsic to the graft wall being critical MCP-1 producers. These findings underscore the importance of systemic treatment for anti-MCP-1/CCR2 therapies. |
