Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
J Thorac Cardiovasc Surg. 2012 Aug;144(2):459-66. doi: 10.1016/j.jtcvs.2011.08.043. Epub 2011 Sep 28.
It is hypothesized that an altered turnover of extracellular matrix mediated by matrix metalloproteinases (MMPs) is present in thoracic aortic aneurysms. Here, we analyzed the occurrence of MMPs and MMP inhibitors in ascending aortic aneurysms in patients with bicuspid and tricuspid aortic valves.
Expression of 23 MMPs and their inhibitors was measured in aortic intima/media and adventitia in 109 patients (40 tricuspid, 69 bicuspid, 68 with aortic diameter≥4.5 cm, and 41 with ≤4.0 cm) using Affymetrix Exon arrays (Affymetrix, Santa Clara, Calif). Gene expression was confirmed by quantitative real-time polymerase chain reaction. Principal components analysis was used to study differences in gene expression. Immunohistochemistry was used to study protein expression.
We detected messenger RNA expression for gelatinases (MMP2 and MMP9), stromelysin 3 (MMP11), all membrane bound MMPs (MMP14, MMP15, MMP16, MMP17, MMP24, MMP25), MMP19, MMP21, and MMP28 in ascending aorta. No expression of collagenases was detected. Principal components analysis showed that changes in mRNA expression between dilated and nondilated aorta were mainly detected in patients with tricuspid aortic valves. MMP14 and MMP19 showed higher expression in dilated aortas and MMP19 expression correlated positively to maximal aortic diameter in patients with tricuspid aortic valves (Rho=0.61, P=.004, and Rho=0.57, P=.008, using raw and body surface area-corrected aortic diameter, respectively). Immunohistochemical staining demonstrated increased medial expression of MMP14 and MMP19 in dilated aorta.
The present study identifies MMP14 and MMP19 as proteolytic enzymes potentially involved in aneurysm formation in the ascending aorta of patients with tricuspid aortic valves.
据推测，基质金属蛋白酶（MMPs）介导的细胞外基质的周转率改变存在于胸主动脉瘤中。在这里，我们分析了二叶式和三叶式主动脉瓣患者升主动脉瘤中 MMPs 和 MMP 抑制剂的发生情况。
使用 Affymetrix Exon 芯片（Affymetrix，圣克拉拉，加利福尼亚州）在 109 名患者的主动脉内膜/中膜和外膜中测量了 23 种 MMPs 和它们的抑制剂的表达（40 例三叶式，69 例二叶式，68 例主动脉直径≥4.5cm，41 例≤4.0cm）。通过定量实时聚合酶链反应证实基因表达。使用主成分分析来研究基因表达的差异。免疫组织化学用于研究蛋白质表达。
我们在升主动脉中检测到明胶酶（MMP2 和 MMP9）、基质溶解素 3（MMP11）、所有膜结合 MMPs（MMP14、MMP15、MMP16、MMP17、MMP24、MMP25）、MMP19、MMP21 和 MMP28 的信使 RNA 表达。未检测到胶原酶的表达。主成分分析表明，扩张和非扩张主动脉之间 mRNA 表达的变化主要在三叶式主动脉瓣患者中检测到。MMP14 和 MMP19 在扩张的主动脉中表达较高，MMP19 的表达与三叶式主动脉瓣患者的最大主动脉直径呈正相关（Rho=0.61，P=.004 和 Rho=0.57，P=.008，分别使用原始和体表面积校正的主动脉直径）。免疫组织化学染色显示扩张的主动脉中 MMP14 和 MMP19 的中膜表达增加。
本研究确定 MMP14 和 MMP19 为潜在参与三叶式主动脉瓣患者升主动脉动脉瘤形成的蛋白水解酶。
