O'Brien E R, Garvin M R, Stewart D K, Hinohara T, Simpson J B, Schwartz S M, Giachelli C M
Department of Pathology, University of Washington School of Medicine, Seattle.
Arterioscler Thromb. 1994 Oct;14(10):1648-56. doi: 10.1161/01.atv.14.10.1648.
How an atherosclerotic plaque evolves from minimal diffuse intimal hyperplasia to a critical lesion is not well understood. Cellular proliferation is a relatively infrequent and modest event in both primary and restenotic coronary atherectomy specimens, leading us to believe that other processes, such as the formation of extracellular matrix, cell migration, neovascularization, and calcification might be more important for lesion formation. The investigation of proteins that are overexpressed in plaque compared with the normal vessel wall may provide clues that will help determine which of these processes are key to lesion pathogenesis. One such molecule, osteopontin (OPN), is an arginine-glycine-aspartate-containing acidic phosphoprotein recently shown to be a novel component of human atherosclerotic plaques and selectively expressed in the rat neointima following balloon angioplasty. Using in situ hybridization and immunohistochemical methods, we demonstrate that in addition to macrophages, smooth muscle and endothelial cells synthesize OPN mRNA and protein in human coronary atherosclerotic plaque specimens obtained by directional atherectomy. In contrast, OPN mRNA and protein were not detected in nondiseased vessel walls. Furthermore, extracellular OPN protein collocalized with sites of early calcification in the plaque that were identified with a sensitive modification of the von Kossa staining technique. These findings, combined with studies showing that OPN has adhesive, chemotactic, and calcium-binding properties, suggest that OPN may contribute to cellular accumulations and dystrophic calcification in atherosclerotic plaques.
动脉粥样硬化斑块如何从微小的弥漫性内膜增生发展为临界病变，目前尚不清楚。在原发性和再狭窄冠状动脉旋切标本中，细胞增殖相对少见且程度较轻，这使我们相信其他过程，如细胞外基质形成、细胞迁移、新生血管形成和钙化，可能对病变形成更为重要。研究与正常血管壁相比在斑块中过度表达的蛋白质，可能会提供线索，有助于确定这些过程中哪些是病变发病机制的关键。一种这样的分子，骨桥蛋白（OPN），是一种含精氨酸-甘氨酸-天冬氨酸的酸性磷蛋白，最近被证明是人类动脉粥样硬化斑块的一种新成分，并在球囊血管成形术后在大鼠新生内膜中选择性表达。使用原位杂交和免疫组化方法，我们证明，除了巨噬细胞外，平滑肌和内皮细胞在通过定向旋切术获得的人类冠状动脉粥样硬化斑块标本中合成OPN mRNA和蛋白。相比之下，在无病变的血管壁中未检测到OPN mRNA和蛋白。此外，细胞外OPN蛋白与斑块中早期钙化部位共定位，这些部位是通过对冯·科萨染色技术的敏感改良鉴定出来的。这些发现，结合显示OPN具有黏附、趋化和钙结合特性的研究，表明OPN可能有助于动脉粥样硬化斑块中的细胞聚集和营养不良性钙化。
