Elevations of tissue-type plasminogen activator and differential expression of urokinase-type plasminogen activator in diseased aorta.
Elevations of tissue-type plasminogen activator and differential expression of urokinase-type plasminogen activator in diseased aorta.
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病变主动脉中组织型纤溶酶原激活剂的升高和尿激酶型纤溶酶原激活剂的差异表达。
DOI：
10.1016/s0741-5214(97)70333-1
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发表时间：
1997
影响因子：
4.3
通讯作者：
H. Kwaan
中科院分区：
文献类型：
--
作者：
P. Shireman;Walter J. McCarthy;William H. Pearce;V. Shively;M. Cipollone;H. Kwaan
目的纤溶酶的升高与腹主动脉瘤（AAA）的发病有关，因为它具有消化细胞外基质蛋白的能力。纤溶酶原激活剂调节纤溶酶原向纤溶酶的转化。组织型纤溶酶原激活物（tPA）在纤溶调节中更重要，而尿激酶型纤溶酶原激活物（uPA）在组织重塑中占主导地位。本研究的目的是确定纤溶酶原激活剂在患病的主动脉的水平，因为他们可能是负责增加纤溶酶水平先前所述的AAA。MethodsLevels的tPA和uPA在AAA，闭塞，和正常（器官供体）主动脉进行了研究，在组织外植体上清液。采用酶联免疫吸附试验测定上清液tPA和uPA水平。结果主动脉闭塞组和AAA组主动脉组织培养上清中tPA含量分别为（20 ± 4）ng/ml和（23 ± 8）ng/ml，但均高于正常组（7 ± 5）ng/ml（P < 0.005）和（P < 0.001）。相反，uPA上清液水平差异表达，AAA中存在最高水平（9.7 ± 2.7 ng/ml），其次是闭塞性（4.9 ± 3.5），正常主动脉中最低水平（1.2 ± 0.7;正常与闭塞性p <0.05，正常与AAA p < 0.001，闭塞性与AAA p < 0.005）。分别通过加入环己酰胺或放线菌素D抑制蛋白质或RNA合成，显示处理和对照上清液之间无显著差异，表明增加是由蛋白质释放而不是活性合成引起的。uPA mRNA水平与上清液uPA水平呈相同趋势（AAA 1.07 ± 0.54，闭塞0.54 ± 0.08，正常主动脉0.01 ± 0.01）。结论动脉瘤和闭塞主动脉中tPA水平相似，但比正常主动脉增加三倍，提示tPA的升高与动脉粥样硬化和闭塞性疾病中存在的动脉硬化有关。所有三组之间uPA水平差异显著，AAA中水平最高，正常标本中水平最低。对uPA mRNA的北方分析也遵循相同的趋势，表明uPA的增加可能在转录水平上受到调节。由于uPA在组织重塑中起着重要作用，我们的研究结果也可能反映了这三种类型标本中的相对组织修复活动，并可能解释先前报道的AAA中纤溶酶水平升高。（J Vasc Surg 1997;25：157-64.）
PurposeElevations of plasmin have been implicated in the pathogenesis of abdominal aortic aneurysms (AAA) because of its ability to digest extracellular matrix proteins. Plasminogen activators regulate the conversion of plasminogen to plasmin. Tissue-type plasminogen activator (tPA) is more important in modulation of fibrinolysis, and urokinase-type plasminogen activator (uPA) is predominant in tissue remodeling. The purpose of this study was to determine the levels of plasminogen activators in diseased aorta because they may be responsible for the increased plasmin levels previously described in AAA.MethodsLevels of tPA and uPA in AAA, occlusive, and normal (organ donor) aorta were studied in tissue explant supernatants. Supernatant tPA and uPA levels were measured with an enzyme-linked immunosorbent assay. Northern analysis was used to quantitate uPA messenger RNA (mRNA) levels in aortic tissue.ResultsLevels of tPA in the supernatants were similar in occlusive (20 ± 4 ng/ml) and AAA (23 ± 8) aorta, but threefold higher than in normal aorta (7 ± 5; p < 0.005 for normal vs occlusive and p < 0.001 for normal vs AAA). In contrast, uPA supernatant levels were differentially expressed, with the highest level existing in AAA (9.7 ± 2.7 ng/ml), followed by occlusive (4.9 ± 3.5), and the lowest levels in normal aorta (1.2 ± 0.7; p < 0.05 for normal vs occlusive, p < 0.001 for normal vs AAA, and p < 0.005 for occlusive vs AAA). Inhibition of protein or RNA synthesis by addition of cyclohexamide or actinomycin D, respectively, revealed no significant difference between treated and control supernatants, suggesting that the increases were caused by protein release rather than active synthesis. Levels of uPA mRNA followed the same trend as the supernatant uPA levels (AAA 1.07 ± 0.54, occlusive 0.54 ± 0.08, and normal aorta 0.01 ± 0.01).ConclusionsLevels of tPA were similar in aneurysmal and occlusive aorta, but exhibited a threefold increase over normal aorta, suggesting that the elevations of tPA are associated with the arteriosclerosis present in both aneurysmal and occlusive disease. Differences in uPA levels were significant between all three groups, with the highest levels in AAA and the lowest levels in normal specimens. Northern analysis of uPA mRNA followed the same trend, suggesting that the increase in uPA may be regulated at the level of transcription. As uPA plays an important role in tissue remodeling, our findings may also reflect the relative tissue repair activities in these three types of specimens and may explain the previously reported increased levels of plasmin seen in AAA. (J Vasc Surg 1997;25:157-64.)
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DOI：
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