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

Abstract

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 ¼ 6), 3 (n ¼ 5), or 6 (n ¼ 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 ¼ 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.

Macrophage activation in response to shape memory polymer foam‐coated aneurysm occlusion devices

“…The porous structure is hypothesized to serve as a scaffold that promotes stable clot formation and provides support for the remodeling of this clot to a connective tissue matrix. There is a growing body of evidence that biomaterials and variations of their structure and chemical properties may influence the phenotype of macrophages responding to the implant 15–21 . Increased surface roughness and increased interconnected porosity are both documented drivers of M2‐like activation, and a pro‐regenerative macrophage phenotype 30,31 .…”

“…There is a growing body of evidence that biomaterials and variations of their structure and chemical properties may influence the phenotype of macrophages responding to the implant. [15][16][17][18][19][20][21] Increased surface roughness and increased interconnected porosity are both documented drivers of M2-like activation, and a pro-regenerative macrophage phenotype. 30,31 Some studies have suggested that the macrophage phenotypes present in the foreign body response may determine the outcome of the implant.…”

“…Interestingly, immunohistochemical analysis of dome resections of ruptured aneurysms demonstrate a strong association with pro‐inflammatory M1 macrophage activation 17–19 . In fact, in a rabbit elastase aneurysm model treated with embolized platinum coils, an M2‐like pro‐healing macrophage activation was correlated with better histological scores and collagen deposition 20 . Together, these studies suggest that M2‐like pro‐regenerative macrophage activation may promote better healing and prevent aneurysm rupture.…”

“…[17][18][19] In fact, in a rabbit elastase aneurysm model treated with embolized platinum coils, an M2-like pro-healing macrophage activation was correlated with better histological scores and collagen deposition. 20 Together, these studies suggest that M2-like pro-regenerative macrophage activation may promote better healing and prevent aneurysm rupture.…”

Degrees of macrophage‐facilitated healing in aneurysm occlusion devices

“…Macrophages are key players in the wound healing response following embolization of aneurysms. 24 Macrophages exist in a continuum of activation states, flanked on either end by pro-inflammatory (M1-like) and prohealing (M2-like) activation. Macrophages also secrete a variety of soluble cues to coordinate the wound healing response in other cell types, especially fibroblasts.…”