Abstract 15250: Vascular Smooth Muscle Cell-Derived Inflammatory Cells Contribute to Aortic Inflammation in Murine Aortic Aneurysms
Introduction: Macrophages thought to be derived from circulating leukocytes play a critical role in inflammation in aortic aneurysms (AA). Vascular smooth muscle cells (SMCs) are known to modulate into an inflammatory state early in AA development. We hypothesize that many of these macrophages in the vessel wall in AA are derived from resident SMCs. It is also unknown if these macrophages take on a pro-inflammatory (M1) or anti-inflammatory state (M2).
Methods: Smooth muscle specific Myh11-CreERT2 mice were bred with ROSA26 STOP-floxEYFP+/+ mice to fate map vascular smooth muscle cells within the aortic wall. Aortic aneurysms were created using an aortic elastase perfusion model (n=7). At 14 days, aortas were harvested, and high-resolution, z-stacking confocal immunofluorescent microscopy was performed to examine the localization of smooth muscle specific eYFP, smooth muscle α actin, and inflammatory cell markers (macrophages: Mac-2, T cells: CD54 and neutrophils: Ly6).
Results: All mice developed aortic aneurysms with an average aortic dilation of (102% ± 7%). By confocal immunohistochemistry, cells were identified in the media with colocalization of smooth muscle cell specific eYFP genetic marker, SMA, and macrophage markers (Mac2)(Figure 1a). Cells were identified expressing smooth muscle cell markers (eYFP, SMA) and both M1 markers (MCP-1, IL1-β) and M2 markers (Arg-1). Of the total macrophage population observed, 40.8% (SD ± 17.7%) of macrophages co-expressed eYFP indicating SMC lineage. In addition, SMC-derived cells expressing T-cell markers (CD4, CD3) were observed. Neutrophil markers did not co-localize with eYFP+ cells.
Conclusions: Roughly 40% of macrophage inflammatory infiltrate in the aortic wall in aneurysms are derived from vascular SMCs. Both pro and anti-inflammatory macrophages are present in the wall of AAs. Understanding the mechanisms that modulate the transformation of SMCs may present novel therapies for treatment of AA disease.
- © 2013 by American Heart Association, Inc.