Crowther M, Goodall S, Jones J L, Bell P R, Thompson M M
Departments of Surgery and Pathology, Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK.
Br J Surg. 2000 Oct;87(10):1391-400. doi: 10.1046/j.1365-2168.2000.01554.x.
Current research has shed new light on the role of matrix metalloproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the production of the MMP-2-MT1-MMP-tissue inhibitor of metalloproteinases (TIMP) 2 system within the wall of aortic aneurysms and in age-matched control arterial tissue.
Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression of MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hybridization and in situ zymography.
All components of the MMP-2-TIMP-2-MT1-MMP enzyme system were detected in the arterial wall of both aneurysm and control samples, specifically in the medial tissue. The enzymes co-localized with medial smooth muscle cells. Gelatinolytic activity was localized to elastin fibres in normal and aneurysmal aorta.
The presence of MT1-MMP within the media of arterial tissue suggests a powerful pathway for the activation of MMP-2. The localization of the MMP-2-TIMP-2-MT1-MMP enzyme system to the medial layer of the arterial wall gives support to the concept that this system may play an aetiological role in the pathogenesis of AAAs.
目前的研究为基质金属蛋白酶(MMP)2在腹主动脉瘤(AAA)发展中的作用带来了新的认识。MMP-2是小动脉瘤壁中的主要蛋白酶,与正常对照相比,源自AAA的平滑肌细胞产生的MMP-2水平升高。在体内,MMP-2以无活性的酶原形式产生,主要由细胞膜结合酶膜型1基质金属蛋白酶(MT1-MMP)激活。本研究调查了主动脉瘤壁和年龄匹配的对照动脉组织中MMP-2-MT1-金属蛋白酶组织抑制剂(TIMP)2系统的产生情况。
使用免疫组织化学、原位杂交和原位酶谱法,对4例主动脉瘤患者的动脉组织和4个年龄匹配的主动脉样本进行MMP-2、TIMP-2和MT1-MMP蛋白的产生和表达检测。
在动脉瘤和对照样本的动脉壁中均检测到MMP-2-TIMP-2-MT1-MMP酶系统的所有成分,特别是在内膜组织中。这些酶与内膜平滑肌细胞共定位。明胶酶活性定位于正常和动脉瘤主动脉的弹性纤维。
动脉组织中膜内存在MT1-MMP提示了一条激活MMP-2的强大途径。MMP-2-TIMP-2-MT1-MMP酶系统定位于动脉壁的中层,支持了该系统可能在AAA发病机制中起病因学作用的观点。