Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong, China.
Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas.
J Surg Res. 2014 Jun 15;189(2):348-58. doi: 10.1016/j.jss.2014.03.027. Epub 2014 Mar 19.
Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) can lead to aortic wall failure. We hypothesized that patients with aneurysms resulting from chronic descending thoracic aortic dissection have elevated tissue and plasma levels of specific MMPs and decreased tissue levels of TIMPs.
Aortic tissue was obtained from 25 patients who required surgical repair of descending thoracic aortic aneurysm due to chronic aortic dissection and from 17 organ-donor controls without aortic disease. Tissue levels of MMP-1, -2, -3, -9, -12, and -13 and TIMP-1 and -2 were measured by colorimetric activity assay or enzyme-linked immunosorbent assay and confirmed by Western blot and immunohistochemistry. Blood obtained from the 25 patients and 15 controls without aortic diseases was used to compare plasma levels of MMP-3, -9, and -12.
Total MMP-1, total MMP-9, and active MMP-9 levels were higher and total MMP-2 levels were lower in dissection tissue than in control tissue. Additionally, the MMP-9 to TIMP-1 and active to total MMP-2 ratios were higher and the MMP-2 to TIMP-2 ratio was lower in dissection tissue. Furthermore, patients had higher plasma active to total MMP-9 ratios than the controls. Age and hypertension were associated with increased MMP levels.
Increased levels of several MMPs and increased MMP to TIMP ratios in aortic tissue from patients suggest an environment that favors proteolysis, which may promote progressive extracellular matrix destruction and medial degeneration after aortic dissection. An elevated active to total MMP-9 ratio in plasma may be a biomarker for end-stage aneurysm development in patients with chronic thoracic aortic disease.
基质金属蛋白酶（MMPs）与基质金属蛋白酶抑制剂（TIMPs）之间的失衡可导致主动脉壁衰竭。我们假设，由于慢性降主动脉夹层引起的动脉瘤患者，其组织和血浆中特定 MMP 的水平升高，而组织中 TIMP 的水平降低。
从 25 名因慢性主动脉夹层而行降主动脉瘤外科修复的患者和 17 名无主动脉疾病的器官供体对照者中获得主动脉组织。通过比色活性测定法或酶联免疫吸附测定法测量 MMP-1、-2、-3、-9、-12 和 -13 以及 TIMP-1 和 -2 的组织水平，并通过 Western blot 和免疫组织化学进行验证。从 25 名患者和 15 名无主动脉疾病的对照者中获得的血液用于比较 MMP-3、-9 和 -12 的血浆水平。
与对照组织相比，夹层组织中的总 MMP-1、总 MMP-9 和活性 MMP-9 水平更高，总 MMP-2 水平更低。此外，夹层组织中 MMP-9 与 TIMP-1 的比值和活性 MMP-2 与总 MMP-2 的比值更高，而 MMP-2 与 TIMP-2 的比值更低。此外，患者的血浆中活性与总 MMP-9 的比值高于对照组。年龄和高血压与 MMP 水平的升高有关。
主动脉组织中几种 MMP 水平升高和 MMP 与 TIMP 比值升高提示有利于蛋白水解的环境，这可能促进主动脉夹层后的细胞外基质进行性破坏和中膜退变。血浆中升高的活性与总 MMP-9 比值可能是慢性胸主动脉疾病患者终末期动脉瘤发展的生物标志物。
