Gelatinase activity and the occurrence of cerebral aneurysms
Gelatinase activity and the occurrence of cerebral aneurysms
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DOI：
10.1161/01.str.28.4.799
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发表时间：
1997-04-01
期刊：
影响因子：
8.3
通讯作者：
Lewis, I
中科院分区：
文献类型：
--
作者：
Chyatte, D;Lewis, I
背景和目的脑动脉瘤与动脉胶原含量减少有关;然而，这种缺乏是由于胶原合成受损还是胶原降解增强所致尚不清楚。本研究测试的假设，增强胶原降解，而不是受损的胶原合成，是与发生脑aneurysm.Methods培养的皮肤成纤维细胞和血清样本进行了研究，在动脉瘤（n=31）和对照组（n=14）的血管造影证据的患者。III型胶原基因的转录通过使用由从汇合培养的成纤维细胞收获的RNA制备的北方印迹来评估。III型胶原蛋白的翻译通过对培养的皮肤成纤维细胞产生的蛋白质进行Western印迹分析来评估。通过放射免疫测定法评估条件组织培养基和血清中I型（PICP）和III型（PIIINP）前胶原肽的胶原代谢。我们评估了血清和条件组织培养液中的胶原降解明胶酶活性，采用定量zymography.Results评估III型胶原合成动脉瘤和对照组患者是相同的。动脉瘤和对照患者成纤维细胞之间III型胶原mRNA的分子量和相对量均无差异。Western印迹分析显示动脉瘤和对照细胞合成的III型前胶原的相对量或分子量没有差异。与对照组相比，动脉瘤患者的天然血清明胶酶活性增加了3倍（P= 0.004）。这种增加沿着胶原代谢增加的血清证据。动脉瘤患者血清PICP（P=.03）和PIIINP（P=.02）水平降低。血清明胶酶活性升高和胶原代谢改变不能用培养的成纤维细胞明胶酶分泌增强或成纤维细胞胶原净合成改变来解释。高血清明胶酶活性是更常见的男性比女性（P= 0.04）。结论这些研究结果是一致的假设，加速酶降解的胶原蛋白和其他结构蛋白损害的机械完整性的脑血管壁，并导致有利于动脉瘤形成的条件。
Background and Purpose Cerebral aneurysms are associated with decreased arterial collagen content; however, whether this deficiency results from impaired collagen synthesis or enhanced collagen degradation is unknown. This study tested the hypothesis that enhanced collagen degradation, not impaired collagen synthesis, is associated with the occurrence of cerebral aneurysms.Methods Cultured skin fibroblasts and serum samples were studied in patients with angiographic evidence of aneurysm (n=31) and control subjects (n=14). Transcription of the type III collagen gene was assessed with the use of Northern blots prepared from RNA harvested from confluent cultured fibroblasts. Translation of type III collagen was assessed by Western blot analysis of proteins produced by cultured skin fibroblasts. Collagen metabolism was assessed by radioimmunoassay for type I (PICP) and type III (PIIINP) procollagen peptides in conditioned tissue culture media and serum. We assessed collagen degradation in serum and conditioned tissue culture media by evaluating gelatinase activity using quantitative zymography.Results Type III collagen synthesis was the same in aneurysm and control patients. Neither the molecular weight nor the relative amount of type III collagen mRNA differed between aneurysm and control patient fibroblasts. Western blot analysis revealed no difference in the relative amount or molecular weight of procollagen III synthesized by aneurysm and control cells. Aneurysm patients had a threefold increase in native serum gelatinase activity compared with control subjects (P=.004). This increase occurred along with serum evidence of increased collagen metabolism. Serum levels of PICP (P=.03) and PIIINP (P=.02) were decreased in aneurysm patients. Elevated serum gelatinase activity and altered collagen metabolism could not be explained by enhanced secretion of gelatinase by cultured fibroblasts or altered net collagen synthesis by fibroblasts. High serum gelatinase activity was more common in men than in women (P=.04).Conclusions These findings are consistent with the hypothesis that accelerated enzymatic degradation of collagens and other structural proteins compromises the mechanical integrity of the cerebral vessel wall and leads to conditions that favor aneurysm formation.