Oemar B S, Werner A, Garnier J M, Do D D, Godoy N, Nauck M, März W, Rupp J, Pech M, Lüscher T F
Division of Cardiology, University Hospital Bern, Switzerland.
Circulation. 1997 Feb 18;95(4):831-9. doi: 10.1161/01.cir.95.4.831.
Atherosclerosis affects certain but not all vascular beds of the human circulation. Its molecular mechanisms are only partially understood. Human connective tissue growth factor (hCTGF) is a novel cysteine-rich, secreted polypeptide. hCTGF is implicated in connective tissue formation, which may play an important role in atherosclerosis.
By using a differential cloning technique, we isolated a cDNA clone from a human aorta cDNA library, which is identical to hCTGF. Northern analysis shows that hCTGF mRNA was expressed at 50- to 100-fold higher levels in atherosclerotic blood vessels compared with normal arteries. In vascular smooth muscle cells, high-level expression of hCTGF mRNA was induced by transforming growth factor-beta 1. Using in situ hybridization and immunohistochemistry, we found that all advanced atherosclerotic lesions of human carotid arteries (eight patients; mean age, 69; age range, 57 to 85 years) and femoral arteries (two patients; mean age, 71.5 years) that we tested expressed high levels of both hCTGF mRNA and protein. hCTGF expression was localized mainly to smooth muscle cells in the plaque lesions that are negative for proliferating cell nuclear antigen staining. In addition, some CD-31-positive endothelial cells of plaque vessels expressed high levels of hCTGF mRNA and protein. hCTGF-positive cells were found predominantly in areas with extracellular matrix accumulation and fibrosis. In contrast, in normal arteries, we were unable to detect either hCTGF mRNA or immunoreactive hCTGF protein.
In the present study, we have shown for the first time that both hCTGF mRNA and protein are expressed in human arteries in vivo and that hCTGF may represent a novel factor expressed at high levels specifically in advanced lesions and may play a role in the development and progression of atherosclerosis.
动脉粥样硬化影响人体循环中的某些而非全部血管床。其分子机制仅部分为人所知。人结缔组织生长因子（hCTGF）是一种新的富含半胱氨酸的分泌型多肽。hCTGF与结缔组织形成有关，这可能在动脉粥样硬化中起重要作用。
通过差异克隆技术，我们从人主动脉cDNA文库中分离出一个与hCTGF相同的cDNA克隆。Northern分析显示，与正常动脉相比，hCTGF mRNA在动脉粥样硬化血管中的表达水平高50至100倍。在血管平滑肌细胞中，转化生长因子-β1可诱导hCTGF mRNA的高水平表达。通过原位杂交和免疫组织化学，我们发现所检测的所有人类颈动脉（8例患者；平均年龄69岁；年龄范围57至85岁）和股动脉（2例患者；平均年龄71.5岁）的晚期动脉粥样硬化病变均表达高水平的hCTGF mRNA和蛋白。hCTGF表达主要定位于增殖细胞核抗原染色阴性的斑块病变中的平滑肌细胞。此外，斑块血管中一些CD-31阳性内皮细胞也表达高水平的hCTGF mRNA和蛋白。hCTGF阳性细胞主要见于细胞外基质积聚和纤维化区域。相反，在正常动脉中，我们无法检测到hCTGF mRNA或免疫反应性hCTGF蛋白。
在本研究中，我们首次表明hCTGF mRNA和蛋白在体内的人动脉中均有表达，并且hCTGF可能是一种在晚期病变中特异性高水平表达的新因子，可能在动脉粥样硬化的发生和发展中起作用。
