Inaba Mayumi, Sugioka Kenichi, Naruko Takahiko, Yunoki Kei, Kato Yasuyuki, Shibata Toshihiko, Inoue Takeshi, Ohsawa Masahiko, Yoshiyama Minoru, Ueda Makiko
Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Hemodial Int. 2014 Jul;18(3):632-40. doi: 10.1111/hdi.12147. Epub 2014 Feb 24.
A high prevalence and a rapid progression of aortic valve stenosis (AS) in patients undergoing hemodialysis (HD) has been reported. In these circumstances, intraleaflet hemorrhage of aortic valve may be related to the development of AS in HD patients. We immunohistochemically examined the relationship among intraleaflet hemorrhage, neovascularization, hemoglobin scavenger receptor (CD163), and heme oxygenase-1 (HO-1) using surgically resected aortic valve specimens from AS patients undergoing HD. The study population consisted of 26 HD patients and 25 non-HD patients with severe AS who had undergone aortic valve replacement. Frozen aortic valve samples surgically obtained from AS patients were stained immunohistochemically with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD31, CD163, and HO-1. Morphometric analysis demonstrated that the CD163-positive macrophage score, the number of CD31-positive microvessels, and the percentage of glycophorin-A and HO-1-positive area were significantly higher in HD patients than in non-HD patients (CD163-positive macrophage score, P < 0.0001; CD31-positive microvessels, P < 0.0001; glycophorin-A, P < 0.0001; HO-1, P < 0.0001). Double immunostaining for CD163 or HO-1 and macrophages revealed that the majority of CD163- or HO-1-positive cells were macrophages. Furthermore, CD163-positive macrophage score was positively correlated with glycophorin-A, HO-1-positive area, and the number of CD31-positive microvessels (glycophorin-A, R = 0.66, P < 0.0001; HO-1, R = 0.50, P < 0.0005; microvessels, R = 0.38, P < 0.01). These findings suggest a positive association among intraleaflet hemorrhage, neovascularization, and enhanced expression of CD163 and HO-1 as a response to intraleaflet hemorrhage in stenotic aortic valves in AS patients undergoing HD.
据报道，接受血液透析（HD）的患者中主动脉瓣狭窄（AS）的患病率较高且病情进展迅速。在这种情况下，主动脉瓣叶内出血可能与HD患者AS的发生有关。我们使用接受HD的AS患者手术切除的主动脉瓣标本，通过免疫组织化学方法研究了叶内出血、新生血管形成、血红蛋白清除受体（CD163）和血红素加氧酶-1（HO-1）之间的关系。研究人群包括26例HD患者和25例接受主动脉瓣置换术的重度AS非HD患者。手术获取的AS患者的冷冻主动脉瓣样本用抗平滑肌细胞、巨噬细胞、血型糖蛋白A（一种红细胞膜特异性蛋白）、CD31、CD163和HO-1的抗体进行免疫组织化学染色。形态计量分析表明，HD患者的CD163阳性巨噬细胞评分、CD31阳性微血管数量以及血型糖蛋白A和HO-1阳性面积百分比均显著高于非HD患者（CD163阳性巨噬细胞评分，P＜0.0001；CD31阳性微血管，P＜0.0001；血型糖蛋白A，P＜0.0001；HO-1，P＜0.0001）。CD163或HO-1与巨噬细胞的双重免疫染色显示，大多数CD163或HO-1阳性细胞为巨噬细胞。此外，CD163阳性巨噬细胞评分与血型糖蛋白A、HO-1阳性面积以及CD31阳性微血管数量呈正相关（血型糖蛋白A，R = 0.66，P＜0.0001；HO-1，R = 0.50，P＜0.0005；微血管，R = 0.38，P＜0.01）。这些发现表明，在接受HD的AS患者狭窄主动脉瓣中，叶内出血、新生血管形成以及CD163和HO-1表达增强之间存在正相关，后者是对叶内出血的一种反应。
