Isik F F, Clowes A W, Gordon D
Department of Surgery, University of Washington Medical Center, Seattle 98195.
Transplantation. 1994 Dec 15;58(11):1246-51.
Elastin is an important component of normal blood vessels and the extracellular matrix of atherosclerotic plaques, but its role in intimal thickening in the arteries of transplanted organs has not been defined. We have looked at elastin gene expression (by in situ mRNA hybridization) in an animal model using an abdominal aortic transplant between 2 strains of rats disparate for MHC class I antigens. The normal aortic wall of adult rats lacks elastin mRNA. Aortic allografts at 7 days after transplantation exhibit increased elastin mRNA in the medial vascular smooth muscle cells. This medial elastin mRNA expression is present only until 20 days after transplantation, and at later times, only the juxtaluminal cells of the neointima express elastin mRNA. Stainable elastin is detectable only in regions that previously demonstrated high levels of elastin mRNA. Combined in situ hybridization and immunocytochemistry reveals that most elastin mRNA-expressing cells in the media are alpha-actin-positive smooth muscle cells. In the neointima, elastin mRNA-expressing cells do not stain with antibodies to either smooth muscle alpha-actin or macrophage proteins. This cell population may represent a "synthetic" phenotype of vascular smooth muscle cell lacking alpha-actin protein. We presume there is immune cell-mediated injury leading to a vascular smooth muscle cell response and part of the vascular smooth muscle cell response may be increased elastin mRNA expression and elastin deposition in the allografts.
弹性蛋白是正常血管以及动脉粥样硬化斑块细胞外基质的重要组成部分，但其在移植器官动脉内膜增厚中的作用尚未明确。我们通过原位mRNA杂交技术，在一种动物模型中研究了弹性蛋白基因的表达情况，该模型采用了两种主要组织相容性复合体（MHC）I类抗原不同的大鼠品系进行腹主动脉移植。成年大鼠的正常主动脉壁缺乏弹性蛋白mRNA。移植后7天的主动脉同种异体移植物，其血管平滑肌细胞中的弹性蛋白mRNA表达增加。这种中层弹性蛋白mRNA表达仅在移植后20天内存在，在之后的时间里，只有新内膜的近腔细胞表达弹性蛋白mRNA。只有在先前显示高水平弹性蛋白mRNA的区域才能检测到可染色的弹性蛋白。原位杂交和免疫细胞化学相结合显示，中层大多数表达弹性蛋白mRNA的细胞是α-肌动蛋白阳性的平滑肌细胞。在新内膜中，表达弹性蛋白mRNA的细胞对平滑肌α-肌动蛋白抗体或巨噬细胞蛋白抗体均无染色反应。这群细胞可能代表缺乏α-肌动蛋白的血管平滑肌细胞的“合成”表型。我们推测存在免疫细胞介导的损伤，导致血管平滑肌细胞反应，并且血管平滑肌细胞反应的一部分可能是同种异体移植物中弹性蛋白mRNA表达增加和弹性蛋白沉积。
