Mast cells associate with neovessels in the media and adventitia of abdominal aortic aneurysms
Received 1 December 2008; accepted 14 March 2009. published online 11 June 2009.
Objective
Mast cells (MCs) are inflammatory cells present in atherosclerotic lesions and neovascularized tissues. Recently, MCs were shown to modulate abdominal aortic aneurysm (AAA) formation in a mouse model. Progression of aneurysmatic disease process may also depend on intraluminal thrombus and neovascularization of the aneurysm wall. Here we investigated the relationship between MCs and inflammation, neovascularization, and the presence of intraluminal thrombus in human AAA.
Methods and Results
Specimens from AAAs and normal control aortas were analyzed with basic histology, immunohistochemical staining, and quantitative real-time polymerase chain reaction (PCR). Double immunostainings with endothelial cell markers CD31/CD34 and MC tryptase showed that, in contrast to histologically normal aorta, MCs in AAA were abundant in the media, but absent from the intima. Medial MCs and (CD31/CD34)+ neovessels increased significantly in AAA compared with normal aorta (P < .0001 for both), and the highest densities of neovessels and MCs were observed in the media of thrombus-covered AAA samples. Also, the proportional thickness of aortic wall penetrated by the neovessels was significantly higher in the AAA samples (P < .0001), and the neovascularized area correlated with the density of medial MCs (P < .0001). In histologic analysis, the medial MCs were mainly located adjacent to the stem cell factor (SCF)+ medial neovessels. Real-time PCR analysis also showed that mRNA levels of genes associated with neovascularization (vascular endothelial growth factor [VEGF], FLT1, VE-cadherin, CD31), and MCs (tryptase, chymase, cathepsin G) were higher in AAA samples than in controls. Demonstration of adhered platelets by CD42b staining and lack of endothelial cell (CD31/CD34) staining in the luminal surface of AAA specimens suggest endothelial erosion of the aneurysm walls.
Conclusions
The results support participation of MCs in the pathogenesis of AAA, particularly regarding neovascularization of aortic wall.
Clinical Relevance
The present results and the results of two recently published studies (Circ Res 2008;102:1368-77 and J Clin Invest 2007;117:3359-68) suggest that MCs may influence AAA pathogenesis by participating in to the regulation of neovascularization and inflammation. Together, these studies have paved the way for studies aiming at modulation of the inflammatory and neoangiogenic response in the AAA. Furthermore, MC activity may be measured using circulating markers such as plasma tryptase, chymase or cathepsin G levels. To date it is unknown whether such markers correlate with the expansion rate and rupture risk of AAA. Thus, new clinical trials are required.
bDepartment of Forensic Medicine, University of Helsinki, Helsinki, Finland
cDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
dAtherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Stockholm, Sweden
Reprint requests: Mikko Mäyränpää, MD, PhD, Wihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, Finland
Supported by grants from the Finnish Foundation for Cardiovascular Research (M.I.M.), the Swedish Research Council (12233, 12660), and the Swedish Heart-Lung foundation and the EC Seventh Framework Programme (FAD-200647) and supported by the Marie Curie Early Stage Research Training Fellowship of the European Community's Sixth Framework Programme, contract number 504926 (J.A.T.).
Competition of interest: none.
Additional material for this article may be found online at www.jvascsurg.org.
ABSTRACT