Background We have previously shown that monocyte chemotactic protein-1 (MCP-1) promotes aneurysm healing.
Objective To determine the temporal cascade and durability of aneurysm healing.
Methods Murine carotid aneurysms were treated with MCP-1-releasing or poly(lactic-co-glycolic) acid (PLGA)-only coils. Aneurysm healing was assessed by quantitative measurements of intraluminal tissue ingrowth on 5 μm sections by blinded observers.
Results Aneurysm healing occurred in stages characteristic of normal wound healing. The 1st stage (day 3) was characterized by a spike in neutrophils and T cells. The 2nd stage (week 1) was characterized by an influx of macrophages and CD45+ cells significantly greater with MCP-1 than with PLGA (p<0.05). The third stage (week 2–3) was characterized by proliferation of smooth muscle cells and fibroblasts (greater with MCP-1 than with PLGA, p<0.05). The fourth stage (3–6 months) was characterized by leveling off of smooth muscle cells and fibroblasts. M1 macrophages were greater at week 1, whereas M2 macrophages were greater at weeks 2 and 3 with MCP-1 than with PLGA. Interleukin 6 was present early and increased through week 2 (p<0.05 compared with PLGA) then decreased and leveled off through 6 months. Tumour necrosis factor α was present early and remained constant through 6 months. MCP-1 and PLGA treatment had similar rates of tissue ingrowth at early time points, but MCP-1 had a significantly greater tissue ingrowth at week 3 (p<0.05), which persisted for 6 months.
Conclusions The sequential cascade is consistent with an inflammatory model of injury, repair, and remodeling.
- Vessel Wall
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Contributors BLH conceived the concept and design, interpreted the data, and drafted the article. HZF, SH, ML, LL acquired the data. KH conceived the design, interpreted the data, and revised the article critically for important intellectual content.
Funding This work was supported by the National Institutes of Health (NIH) grant number R01 NS083673.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Unpublished data are available for data sharing with the permission of the corresponding author.