Mast cells associate with neovessels in the media and adventitia of abdominal aortic aneurysms
Mast cells associate with neovessels in the media and adventitia of abdominal aortic aneurysms
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DOI：
10.1016/j.jvs.2009.03.055
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发表时间：
2009-08-01
影响因子：
4.3
通讯作者：
Hedin, Ulf
中科院分区：
文献类型：
--
作者：
Mayranpaa, Mikko I.;Trosien, Julia A.;Hedin, Ulf
目的：肥大细胞(Mast cell，MC)是存在于动脉粥样硬化病变和新生血管组织中的炎性细胞。最近，在一种小鼠模型中，巨噬细胞被证明能够调节腹主动脉瘤(AAA)的形成。动脉瘤性疾病的进展也可能取决于瘤壁的腔内血栓和新生血管。方法和结果：对AAA和正常对照的主动脉标本进行了基本组织学、免疫组织化学染色和实时定量聚合酶链式反应(PCR)分析。内皮细胞标记物CD31/CD34和MC类胰酶双重免疫染色显示，与组织学正常的主动脉相比，AAA的MCs在中层丰富，但在内膜中缺失。AAA患者的中膜MCs和(CD31/CD34)(+)细胞数均显著高于正常对照组(P均<0.0001)，且血栓覆盖的AAA患者的中膜MCs和MCs密度最高。AAA组新生血管穿透主动脉壁的比例明显增加(P<；.0001)，新生血管面积与中膜MC密度呈正相关(P<；.0001)。在组织学分析中，内侧MC主要位于尾状细胞因子(SCF)(+)的内侧新生血管附近。实时荧光定量聚合酶链式反应分析还显示，AAA组织中与新生血管相关的基因(血管内皮生长因子[VEGF]、Flt1、VE-cadherin、CD31)和MC(类胰蛋白酶、糜蛋白酶、组织蛋白酶G)的mRNA水平均高于对照组。AAA标本管腔表面CD42b染色显示血小板黏附，CD31/CD34染色缺失，提示瘤壁内皮细胞侵蚀。结论：MCs参与了AAA的发病机制，尤其是主动脉壁的新生血管。(《血管外科杂志》2009；50：388-96。)
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 stern 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. (J Vasc Surg 2009;50:388-96.)