Expression of matrix metalloproteinase-12 in aortic dissection
Expression of matrix metalloproteinase-12 in aortic dissection
复制标题
基质金属蛋白酶12在主动脉夹层中的表达
DOI：
10.1186/1471-2261-13-34
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发表时间：
2013-05-03
影响因子：
2.1
通讯作者：
Meng, Zhaohui
中科院分区：
文献类型：
--
作者：
Song, Yi;Xie, Yuehui;Meng, Zhaohui
主动脉夹层（AD）是一种大血管的急性过程，具有危险的致病条件和高致残率和高死亡率。阿尔茨海默病的发病机制仍有争议。基质金属蛋白酶-12 （Matrix metalloproteinase-12, MMP-12）参与腹主动脉瘤、动脉粥样硬化、肺气肿、癌症等多种病理过程。然而，这种弹性酶很少在AD的情况下被评估。本研究的目的是研究MMP-12在主动脉组织中的表达，以便更好地了解AD的可能机制。方法分别采用逆转录聚合酶链反应（RT-PCR）、Western blot、免疫组织化学、荧光共振能量转移（FRET）活性测定和酶联免疫吸附试验（ELISA）分析比较主动脉组织和血清样品中MMP-12的蛋白表达水平。从12例主动脉置换术时的急性Stanford a夹层患者和4例冠状动脉疾病（CAD）行冠状动脉搭桥手术的患者中获取升主动脉组织标本。同时，从15名急性斯坦福a型夹层患者和10名健康个体作为对照组收集血清样本。结果AD组和CAD组均能检测到smmp -12活性，但AD组smmp -12活性高于CAD组（P < 0.05）。AD组和健康组血清样品均存在MMP-12蛋白水解，且AD组活性水平明显高于健康组（P < 0.05）。AD患者血清中MMP-12活性高于主动脉壁（P < 0.05）。MMP抑制剂v可抑制主动脉壁组织中MMP-12的活性（P < 0.05）。结论本研究直接证实了主动脉夹层患者的主动脉标本和血液样本中存在MMP-12蛋白水解活性。MMP-12可能作为血管损伤和修复的临床诊断工具和治疗靶点具有潜在的相关性。
BackgroundAortic dissection(AD) is an acute process of large blood vessels characterized by dangerous pathogenic conditions and high disability and high mortality. The pathogenesis of AD remains debated. Matrix metalloproteinase-12 (MMP-12) participates in many pathological processes such as abdominal aortic aneurysm, atherosclerosis, emphysema and cancer. However, this elastase has rarely been assessed in the presence of AD. The aim of the present study was to investigate the expression of MMP-12 in aortic tissue so as to offer a better understanding of the possible mechanisms of AD.MethodsThe protein expression levels of MMP-12 were analyzed and compared in aorta tissue and the blood serum samples by reverse transcription polymerase chain reaction(RT-PCR), Western blotting, immuno-histochemistry, fluorescence resonance energy transfer ( FRET ) activity assay and enzyme-linked immuno sorbent assay ( ELISA ), respectively. Ascending aorta tissue specimens were obtained from 12 patients with an acute Stanford A-dissection at the time of aortic replacement, and from 4 patients with coronary artery disease (CAD) undergoing coronary artery bypass surgery. Meanwhile, serum samples were harvested from 15 patients with an acute Stanford A-dissection and 10 healthy individuals who served as the control group.ResultsMMP-12 activity could be detected in both AD and CAD groups, but the level in the AD group was higher than those in the CAD group (P < 0.05). MMP-12 proteolysis existed in both serum samples of the AD and healthy groups, and the activity level in the AD group was clearly higher than in the healthy group (P < 0.05). For AD patients, MMP-12 activity in serum was higher than in the aorta wall (P < 0.05). MMP-12 activity in the aortic wall tissue can be inhibited by MMP inhibitor v (P < 0.05).ConclusionThe present study directly demonstrates that MMP-12 proteolytic activity exists within the aorta specimens and blood samples from aortic dissection patients. MMP-12 might be of potential relevance as a clinically diagnostic tool and therapeutic target in vascular injury and repair.