The Distribution and Role of M1 and M2 Macrophages in Aneurysm Healing after Platinum Coil Embolization.

BACKGROUND AND PURPOSE: Impairment of macrophage polarization from a proinflammatory macrophage type 1 (M1) population to an anti-inflammatory macrophage type 2 (M2) population is a hallmark of poor wound healing. In this study, we aimed to evaluate the distribution of M1 and M2 macrophages and to analyze their association with healing in aneurysms embolized by endovascular coiling. MATERIALS AND METHODS: Elastase-induced aneurysms were created in female rabbits and subsequently embolized with platinum coils. Aneurysm occlusions were evaluated with angiographic imaging at 1 (n = 6), 3 (n = 5), or 6 (n = 6) months. Aneurysm tissues were harvested for histologic analysis, quantification of M1 and M2 macrophages by immunofluorescence, and collagen deposition determined by Masson trichrome staining. Histologic grading of aneurysm healing was also performed. Untreated aneurysms were used as controls (n = 6). RESULTS: The M1 macrophage population was highest at 1 month posttreatment, progressively decreasing at 3 and 6 months. The M2 macrophage population progressively increased at 3 and 6 months posttreatment. The highest collagen deposition was at 6 months posttreatment. We found a moderate-to-weak direct correlation between the percentage of M2 macrophages and collagen deposition, as well as total histologic scores overall, and a strongly positive direct correlation between the percentage of M2 macrophages and total histologic scores at 6 months posttreatment. CONCLUSIONS: Our data support the direct correlation between M2 macrophage polarization and healing in aneurysm tissues. Our results show a positive relationship between M2 macrophage populations and total histologic scores at later stages of healing after endovascular coiling. We conclude that interventions aimed at stimulating M2 macrophage expression locally may improve aneurysm healing after coil embolization.

Histologic and Biomolecular Similarities in Healing between Aneurysms and Cutaneous Skin Wounds.

The poorly understood mechanisms of aneurysm healing contribute substantially to the pressing medical problem of coiled aneurysm recanalization. Using an established saccular aneurysm model, we developed an animal model system in rabbits to study aneurysm and skin wound healing concurrently in the same animal. We found treated aneurysm healing to be similar to skin wound healing both histologically and in biomarker gene and protein expression, but in a delayed fashion.