Ryer Evan J, Garvin Robert P, Schworer Charles M, Bernard-Eckroth Kamell R, Tromp Gerard, Franklin David P, Elmore James R, Kuivaniemi Helena
Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, Pa.
Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, Pa.
J Vasc Surg. 2015 Nov;62(5):1303-11.e4. doi: 10.1016/j.jvs.2014.04.067. Epub 2014 Jul 3.
The pathogenesis of abdominal aortic aneurysm (AAA) formation includes inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. That multipotent stem cells have an important role in cardiovascular health and disease has been well established, but the role of stem cells in aortic structural deterioration is poorly defined. We sought to describe the presence of stem cells in human AAA tissue and also investigated the differentiation of stem cells within the aneurysmal aorta.
Infrarenal aortic wall specimens were collected from patients (n = 7) undergoing open AAA surgical repair. Nonaneurysmal infrarenal aortic control samples (n = 4) were collected at autopsies. Using immunohistochemistry, we compared the abundance of Stro1-positive ((+)), c-kit(+), and CD34(+) cells in aortic tissue. Using double-immunofluorescence staining, we evaluated stem cell differentiation into smooth muscle cells (SM22), fibroblasts (FSP1), and macrophages (CD68). We then investigated the colocalization of CD68(+) cells with the cellular marker of proliferation Ki67.
The media and adventitia of infrarenal AAA samples both demonstrated a significantly greater number of c-kit(+) and CD34(+) cells compared with matched control nonaneurysmal aortic tissues; however, the abundance of Stro1(+) cells was not significantly different between the groups. Using double-immunofluorescence staining, we identified that AAA stem cells express the macrophage marker CD68 but not the smooth muscle cell marker SM22 or the fibroblast marker FSP1. CD68(+) cells within the aortic wall colocalized with the cellular marker of proliferation Ki67.
Stem cells are significantly elevated in infrarenal AAA tissue compared with matched control aortic tissue. Our data also demonstrate that AAA stem cells express macrophage surface antigens but not smooth muscle cell or fibroblast markers. Furthermore, CD68(+) cells within the aortic wall colocalized with the cellular marker of proliferation Ki67. These finding suggest an inflammatory/immune role of stem cells during AAA pathogenesis and raise the possibility of localized replenishment therapy within the aneurysm wall.
腹主动脉瘤（AAA）形成的发病机制包括炎症、血管平滑肌细胞凋亡、细胞外基质降解和氧化应激。多能干细胞在心血管健康和疾病中发挥重要作用已得到充分证实，但干细胞在主动脉结构退变中的作用尚不明确。我们试图描述人AAA组织中干细胞的存在情况，并研究动脉瘤主动脉内干细胞的分化情况。
从接受开放性AAA手术修复的患者（n = 7）中收集肾下腹主动脉壁标本。在尸检时收集非动脉瘤性肾下腹主动脉对照样本（n = 4）。使用免疫组织化学方法，我们比较了主动脉组织中Stro1阳性（(+)）、c-kit(+)和CD34(+)细胞的丰度。使用双免疫荧光染色，我们评估了干细胞向平滑肌细胞（SM22）、成纤维细胞（FSP1）和巨噬细胞（CD68）的分化情况。然后我们研究了CD68(+)细胞与增殖细胞标志物Ki67的共定位情况。
与匹配的对照非动脉瘤性主动脉组织相比，肾下腹主动脉瘤样本的中膜和外膜均显示出明显更多的c-kit(+)和CD34(+)细胞；然而，两组之间Stro1(+)细胞的丰度没有显著差异。使用双免疫荧光染色，我们发现AAA干细胞表达巨噬细胞标志物CD68，但不表达平滑肌细胞标志物SM22或成纤维细胞标志物FSP1。主动脉壁内的CD68(+)细胞与增殖细胞标志物Ki67共定位。
与匹配的对照主动脉组织相比，肾下腹主动脉瘤组织中的干细胞显著升高。我们的数据还表明，AAA干细胞表达巨噬细胞表面抗原，但不表达平滑肌细胞或成纤维细胞标志物。此外，主动脉壁内的CD68(+)细胞与增殖细胞标志物Ki67共定位。这些发现提示干细胞在AAA发病机制中具有炎症/免疫作用，并增加了在动脉瘤壁内进行局部补充治疗的可能性。
