The involvement of matrix glycoproteins in vascular calcification and fibrosis: an immunohistochemical study
The involvement of matrix glycoproteins in vascular calcification and fibrosis: an immunohistochemical study
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DOI：
10.1002/path.1020
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发表时间：
2002-02-01
影响因子：
7.3
通讯作者：
Roberts, ISD
中科院分区：
文献类型：
--
作者：
Canfield, AE;Farrington, C;Roberts, ISD
钙化和纤维内膜增生与大动脉中的晚期复杂动脉粥样硬化有关，但也可能发生在较小的血管中，导致缺血性组织坏死。本研究旨在探讨不同大小血管的钙化和内膜纤维化机制是否相似。骨桥蛋白（OPN）、基质Gla蛋白（MGP）、血小板反应蛋白-1（TSP-1）和软骨寡聚基质蛋白（COMP）在三种类型的人类血管病变中的定位进行了研究：动脉粥样硬化、肾移植物慢性血管排斥反应（CVR）和钙化性尿毒症小动脉病（钙化耐受）。选择这些病变是因为它们影响不同尺寸的血管，并且它们表现出纤维增生性内膜反应，伴或不伴钙化，导致管腔闭塞和缺血性并发症。正常血管中未检测到OPN、MGP、TSP-1和COMP。然而，OPN和MGP在动脉粥样硬化病变内的钙化部位和钙化耐受的微血管中表达，表明不同大小血管的钙化可能通过共同的机制发生。在纤维内膜增生区域未检测到这些蛋白。与此相反，TSP-1主要定位于动脉粥样硬化病变的纤维组织中，并且也在显示CVR的动脉的扩张的纤维内膜中表达。COMP主要位于大多数晚期动脉粥样硬化病变的脂质核心下的纤维组织内。TSP-1和COMP也在动脉粥样硬化病变的微钙化区域中检测到，TSP-1在钙化耐受的钙化区域附近检测到。然而，TSP-1和COMP均未定位于这些病变内的钙化灶。OPN、MGP、TSP-1和COMP定位于病理性而非正常动脉内膜支持这些蛋白在血管纤维化和钙化的发展中的致病作用。调节它们的产生和活性可能为许多血管疾病的治疗提供新的方法。版权所有（C）2001约翰威利父子有限公司
Calcification and fibrointimal proliferation are associated with advanced complicated atherosclerosis in large arteries but may also occur in smaller vessels, resulting in ischaemic tissue necrosis. This study investigates whether the mechanisms of calcification and intimal fibrosis are similar in vessels of different sizes. The localization of osteopontin (OPN), matrix Gla protein (MGP), thrombospondin-1 (TSP-1), and cartilage oligomeric matrix protein (COMP) was investigated in three types of human vascular lesions: atherosclerosis, chronic vascular rejection (CVR) in renal allografts, and calcific uraemic arteriolopathy (calciphylaxis). These lesions were chosen as they affect different sized blood vessels and they exhibit a fibroproliferative intimal reaction, with or without calcification, resulting in luminal obliteration and ischaemic complications. OPN, MGP, TSP-1, and COMP were not detected in normal blood vessels. However, OPN and MGP were expressed at sites of calcification within atherosclerotic lesions and in microvessels in calciphylaxis, suggesting that calcification in different sized vessels may occur by a common mechanism. These proteins were not detected in areas of fibrointimal proliferation. In contrast, TSP-1 was localized primarily within the fibrous tissue of atherosclerotic lesions and was also expressed in the expanded fibrous intima of arteries showing CVR. COMP was localized primarily within the fibrous tissue under the lipid core of the majority of advanced atherosclerotic lesions. TSP-1 and COMP were also detected in areas of microcalcification in atherosclerotic lesions and TSP-1 was detected adjacent to areas of calcification in calciphylaxis. However, neither TSP-1 nor COMP was localized to calcific foci within these lesions. The localization of OPN, MGP, TSP-1, and COMP to pathological, but not normal arterial intima supports a pathogenetic role for these proteins in the development of vascular fibrosis and calcification. Modulation of their production and activity may offer a novel approach to the therapy of a number of vascular diseases. Copyright (C) 2001 John Wiley Sons, Ltd.