Sinha Indranil, Bethi Siddharth, Cronin Paul, Williams David M, Roelofs Karen, Ailawadi Gorav, Henke Peter K, Eagleton Matthew J, Deeb G Michael, Patel Himanshu J, Berguer Ramon, Stanley James C, Upchurch Gilbert R
Section of Vascular Surgery, University of Michigan, Ann Arbor, MI 48109-0329, USA.
J Vasc Surg. 2006 Feb;43(2):342-8. doi: 10.1016/j.jvs.2005.10.013.
This study was undertaken to define matrix metalloproteinase (MMP) expression in the anterior and posterior wall of descending thoracic aortic aneurysms (TAAs) and correlate it with specific computed tomography (CT) image sites within the descending thoracic aorta.
Serial CT images of patients with TAAs were compared with age- and gender-matched normal descending thoracic aortas at levels T4-T12. The mean circumference of the TAAs was 153 mm (n = 12) and 148 mm (n = 11) at T8 and T10, respectively, compared with 75 mm (n = 12) and 75 mm (n = 10) in controls (P < .001). Aortic tissue was collected from a separate set of eight patients undergoing descending TAA resection (processed < or =12 hours of excision) and six cadavers (processed < or =24 hours of death). Tissue collected between the intercostals arteries was defined as posterior wall, and directly opposite was the anterior wall. MMP-9 and MMP-2 messenger RNA (mRNA) extracted from aortic tissue was analyzed by quantitative real time polymerase chain reaction (PCR) and normalized to beta-actin. Immunohistochemistry was performed for MMP-9 and MMP-2. CT aortic measurements and MMP expression were compared by t tests and analysis of variance, respectively.
The ratio of arc distance between the intercostals on the posterior wall to total aortic circumference was 0.14 in healthy controls compared with 0.08 in TAAs at vertebral level T8 (P = .001). At T10, the ratio was 0.15 in healthy controls compared with 0.11 in TAAs (P = .001). MMP-9 expression in TAAs was 4.3-fold higher in the anterior wall compared with the posterior wall (P = .03). Conversely, MMP-2 expression in TAAs was 3.2-fold higher in the posterior wall compared with the anterior wall (P = .008). MMP expression was not detected in control cadaver aortas.
Anterior walls of expanding TAAs grow at a greater rate than the posterior wall, as determined from the lower ratio of intercostal arc distance to total circumference in TAAs. Differential MMP expression appears to be a biologic marker for asymmetric growth in the TAA wall.
The pathogenesis of thoracic aortic aneurysms (TAAs) is poorly understood. Multiple lines of evidence suggest that matrix metalloproteinases (MMPs), a family of enzymes, are important in aneurysm development. Earlier experiments documented a regional variation of MMP-9 in stimulated rodent aortas, with production greater in the abdominal aorta compared with the thoracic aorta. The present study extends that observation and documents asymmetric aneurysm development in the TAA wall, with increased anterior wall growth in correlation to increased MMP-9 production. An improved understanding of the mechanisms by which MMP production is regulated is critical.
本研究旨在确定降主动脉瘤（TAA）前后壁中基质金属蛋白酶（MMP）的表达情况，并将其与降主动脉内特定的计算机断层扫描（CT）图像部位相关联。
将TAA患者的系列CT图像与年龄和性别匹配的正常降主动脉在T4 - T12水平进行比较。TAA在T8和T10水平的平均周长分别为153 mm（n = 12）和148 mm（n = 11），而对照组分别为75 mm（n = 12）和75 mm（n = 10）（P <.001）。从另一组8例接受降主动脉瘤切除术的患者（切除后处理时间≤12小时）和6具尸体（死亡后处理时间≤24小时）中采集主动脉组织。肋间动脉之间采集的组织定义为后壁，其正对面为前壁。从主动脉组织中提取的MMP - 9和MMP - 2信使核糖核酸（mRNA）通过定量实时聚合酶链反应（PCR）进行分析，并以β - 肌动蛋白进行标准化。对MMP - 9和MMP - 2进行免疫组织化学检测。CT主动脉测量值和MMP表达分别通过t检验和方差分析进行比较。
在T8椎体水平，健康对照组后壁肋间弧距离与主动脉总周长的比值为0.14，而TAA组为0.08（P = 0.001）。在T10水平，健康对照组该比值为0.15，TAA组为0.11（P = 0.001）。TAA前壁的MMP - 9表达比后壁高4.3倍（P = 0.03）。相反，TAA后壁的MMP - 2表达比前壁高3.2倍（P = 0.008）。在对照尸体主动脉中未检测到MMP表达。
从TAA肋间弧距离与总周长的较低比值可确定，扩张性TAA的前壁生长速度比后壁快。MMP表达差异似乎是TAA壁不对称生长的生物学标志物。
胸主动脉瘤（TAA）的发病机制尚不清楚。多条证据表明，基质金属蛋白酶（MMPs）这一酶家族在动脉瘤形成中很重要。早期实验记录了刺激的啮齿动物主动脉中MMP - 9的区域差异，腹主动脉中的产生量比胸主动脉更多。本研究扩展了该观察结果，并记录了TAA壁中动脉瘤的不对称发展，前壁生长增加与MMP - 9产生增加相关。更好地理解MMP产生的调节机制至关重要。
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