Extracellular matrix metalloproteinase inducer (EMMPRIN) is present in smooth muscle cells of human aneurysmal aorta and is induced by angiotensin II in vitro
Extracellular matrix metalloproteinase inducer (EMMPRIN) is present in smooth muscle cells of human aneurysmal aorta and is induced by angiotensin II in vitro
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细胞外基质金属蛋白酶诱导剂 (EMMPRIN) 存在于人动脉瘤主动脉的平滑肌细胞中，并在体外由血管紧张素 II 诱导
DOI：
10.1042/cs20080235
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发表时间：
2009-06-01
期刊：
影响因子：
6
通讯作者：
Chen, Han
中科院分区：
文献类型：
--
作者：
Chen, Xiao-feng;Wang, Jian-an;Chen, Han
本研究的目的是确定EMMPRIN（细胞外基质金属蛋白酶诱导剂）是否存在，并在人类动脉瘤中上调，并评估与AngII（血管紧张素II）诱导的动脉瘤形成的可能关联。通过免疫组织化学，在41例TAA（胸主动脉瘤）（A型主动脉夹层，n = 12; B型主动脉夹层，n = 7;无夹层的TAA，n = 7）或AAA（腹主动脉瘤，n = 15）患者的手术标本中评估EMMPRIN的存在。将主动脉瘤组织中的EMMPRIN表达与尸检期间获得的12个动脉瘤（无任何血管疾病）进行比较，并对染色强度和染色的血管细胞百分比进行评分。通过蛋白质印迹法分析AngII刺激后培养的人主动脉SMC（平滑肌细胞）中的EMMPRIN蛋白水平。在TAA和AAA患者的主动脉瘤病变中检测到显著的EMMPRIN免疫反应性。在平滑肌细胞壁，α-actin阳性的SMC是EMMPRIN的主要来源。伴有夹层的TAA（68.4%）中EMMPRIN过表达的频率显著高于（P = 0.026）未发生夹层的TAA（14.3%）。AngII刺激上调培养的人主动脉SMC中EMMPRIN的表达，其被AT（1）R（AngII 1型受体）拮抗剂losartan抑制。总之，本研究首次报道了EMMPRIN在主动脉瘤样病变中的表达，我们推测EMMPRIN可能在这些疾病的发病机制中起重要作用。这些异常是否是潜在的治疗靶点值得进一步研究。
The aim of the present study was to determine whether EMMPRIN (extracellular matrix metalloproteinase inducer) is present and is up-regulated in human aneurysmal aortas, and to assess a possible association with Angll (angiotensin II)-induced aneurysm formation. The presence of EMMPRIN was assessed in 41 surgical specimens from patients with a TAA (thoracic aortic aneurysm) (Type A aortic dissection, n = 12; Type B aortic dissection, n = 7; and TAA without dissection, n = 7) or an AAA (abdominal aortic aneurysm, n = 15) by immunohistochemistry. EMMPRIN expression in aortic aneurysm tissues was compared with 12 aortas obtained during autopsy (free of any vascular diseases), and scored for both staining intensity and the percentage of vascular cells stained. EMMPRIN protein levels in cultured human aortic SMCs (smooth muscle cells) following stimulation of Angll were analysed by Western blotting. Significant EMMPRIN immunoreactivity was detected in aortic aneurysm lesions from patients with TAAs and AAAs. In the aneurysmal wall, alpha-actin-positive SMCs were the main source of EMMPRIN. The frequency of EMMPRIN overexpression was significantly higher (P = 0.026) in TAAs with dissection (68.4%) than TAAs without dissection (14.3%). Angll stimulation up-regulated the expression of EMMPRIN in cultured human aortic SMCs, which was suppressed by the addition of the AT(1) R (Angll type 1 receptor) antagonist losartan. In conclusion, the present study is the first to report the expression of EMMPRIN in aortic aneurysmal diseases, and we speculate that EMMPRIN may be important in the pathogenesis of these diseases. Whether these abnormalities are potential therapeutic targets deserve further investigation.