Chyatte D, Lewis I
Cerebrovascular Research Laboratory, Cleveland Clinic Foundation, Ohio 44195, USA.
Stroke. 1997 Apr;28(4):799-804. doi: 10.1161/01.str.28.4.799.
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.
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.
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).
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.
脑动脉瘤与动脉胶原含量降低有关；然而，这种缺乏是由于胶原合成受损还是胶原降解增强尚不清楚。本研究检验了这样一个假设，即与脑动脉瘤发生相关的是胶原降解增强而非胶原合成受损。
对有血管造影证据显示存在动脉瘤的患者（n = 31）和对照受试者（n = 14）的培养皮肤成纤维细胞和血清样本进行了研究。使用从汇合培养的成纤维细胞收获的RNA制备的Northern印迹法评估III型胶原基因的转录。通过对培养的皮肤成纤维细胞产生的蛋白质进行蛋白质印迹分析来评估III型胶原的翻译。通过放射免疫分析法测定条件性组织培养基和血清中I型（PICP）和III型（PIIINP）前胶原肽来评估胶原代谢。我们通过使用定量酶谱法评估明胶酶活性来评估血清和条件性组织培养基中的胶原降解。
动脉瘤患者和对照患者的III型胶原合成相同。动脉瘤患者和成纤维细胞对照患者之间，III型胶原mRNA的分子量和相对量均无差异。蛋白质印迹分析显示，动脉瘤细胞和对照细胞合成的前胶原III的相对量或分子量没有差异。与对照受试者相比，动脉瘤患者的天然血清明胶酶活性增加了两倍（P = 0.004）。这种增加伴随着胶原代谢增加的血清证据。动脉瘤患者的血清PICP（P = 0.03）和PIIINP（P = 0.02）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分泌明胶酶增加或成纤维细胞净胶原合成改变来解释。血清明胶酶活性高在男性中比在女性中更常见（P = 0.04）。
这些发现与以下假设一致，即胶原和其他结构蛋白的酶促降解加速会损害脑血管壁的机械完整性，并导致有利于动脉瘤形成的条件。
