Hovsepian D M, Ziporin S J, Sakurai M K, Lee J K, Curci J A, Thompson R W
Department of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA.
J Vasc Interv Radiol. 2000 Nov-Dec;11(10):1345-52. doi: 10.1016/s1051-0443(07)61315-3.
Matrix metalloproteinase-9 (MMP-9) is abundantly expressed in abdominal aortic aneurysms (AAAs), where it plays a pivotal role in connective tissue destruction. Elevated plasma concentrations of MMP-9 (MMP-9PL) also have been reported in patients with AAAs, but it is unclear if this can distinguish patients with AAAs from those with atherosclerotic occlusive disease (AOD). The purpose of this study was to further define the utility of elevated MMP-9PL levels in the diagnosis and evaluation of AAAs, and to examine if changes in MMP-9PL can be used as a functional biomarker of degenerative aneurysm disease.
Peripheral venous blood was obtained from 25 patients with AAAs, 15 patients with AOD, and five normal control subjects. MMP-9PL levels were determined by an enzyme-linked immunosorbent assay. In four patients undergoing open AAA repair, MMP-9PL levels were directly compared with the amount of MMP-9 produced in aortic tissue. Six additional patients undergoing operative AAA repair were followed for 3-10 months to determine how treatment affected elevated MMP-9PL concentrations.
Mean (+/- SE) MMP-9PL was 36.1 +/- 7.7 ng/mL in normal control subjects, 54.7 +/- 10.5 ng/mL in patients with AOD, and 99.4 +/- 17.4 ng/mL in patients with AAAs (P < .05 versus normal control subjects and patients with AOD). Elevated MMP-9PL levels (> 87.8 ng/mL) were found in 12 of 25 (48%) patients with AAA but in only one of 15 (7%) patients with AOD (P < .05). MMP-9PL levels did not correlate significantly with either age, gender, or aneurysm diameter, although there was a trend toward the highest values in male patients with large AAAs. Production of MMP-9 in aneurysm tissues paralleled MMP-9PL levels, and elevated MMP-9PL levels decreased by 92.7% +/- 3.2% after surgical AAA repair.
Elevated MMP-9PL levels were observed in approximately one half of patients with AAAs and less than 10% of those with AOD (positive predictive value of 92.3%), but normal MMP-9PL levels had limited utility in excluding the presence of an aortic aneurysm (negative predictive value, 52%). MMP-9PL levels in patients with AAAs appeared to directly reflect the amount of MMP-9 produced within aneurysm tissue, and MMP-9PL levels decreased substantially after aneurysm repair. Measures of circulating MMP-9 may provide a biologically relevant marker of connective tissue metabolism in patients with AAAs.
基质金属蛋白酶-9（MMP-9）在腹主动脉瘤（AAA）中大量表达，在结缔组织破坏中起关键作用。也有报道称AAA患者血浆中MMP-9浓度升高（MMP-9PL），但尚不清楚这能否将AAA患者与动脉粥样硬化闭塞性疾病（AOD）患者区分开来。本研究的目的是进一步明确升高的MMP-9PL水平在AAA诊断和评估中的作用，并探讨MMP-9PL的变化是否可作为退行性动脉瘤疾病的功能生物标志物。
采集25例AAA患者、15例AOD患者和5例正常对照者的外周静脉血。采用酶联免疫吸附测定法测定MMP-9PL水平。在4例接受开放性AAA修复的患者中，将MMP-9PL水平与主动脉组织中产生的MMP-9量进行直接比较。另外6例接受手术AAA修复的患者随访3 - 10个月，以确定治疗如何影响升高的MMP-9PL浓度。
正常对照者的平均（±标准误）MMP-9PL为36.1±7.7 ng/mL，AOD患者为54.7±10.5 ng/mL，AAA患者为99.4±17.4 ng/mL（与正常对照者和AOD患者相比，P < 0.05）。25例AAA患者中有12例（48%）MMP-9PL水平升高（> 87.8 ng/mL），而15例AOD患者中只有1例（7%）升高（P < 0.05）。MMP-9PL水平与年龄、性别或动脉瘤直径均无显著相关性，尽管在大AAA男性患者中MMP-9PL水平有最高值的趋势。动脉瘤组织中MMP-9的产生与MMP-9PL水平平行，手术修复AAA后升高的MMP-9PL水平下降了92.7%±3.2%。
约一半的AAA患者MMP-9PL水平升高，而AOD患者中不到10%升高（阳性预测值为92.3%），但正常MMP-9PL水平在排除主动脉瘤存在方面的作用有限（阴性预测值为52%）。AAA患者的MMP-9PL水平似乎直接反映动脉瘤组织中产生的MMP-9量，动脉瘤修复后MMP-9PL水平大幅下降。循环MMP-9的检测可能为AAA患者结缔组织代谢提供生物学相关标志物。
