BALLOON CATHETERIZATION INDUCES ARTERIAL EXPRESSION OF EMBRYONIC FIBRONECTINS
BALLOON CATHETERIZATION INDUCES ARTERIAL EXPRESSION OF EMBRYONIC FIBRONECTINS
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DOI：
10.1161/01.atv.15.11.1958
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发表时间：
1995-11-01
影响因子：
8.7
通讯作者：
VANDEWATER, L
中科院分区：
文献类型：
--
作者：
DUBIN, D;PETERS, JH;VANDEWATER, L
纤连蛋白 (FN) 包含一个粘附细胞外基质蛋白家族，这些蛋白通过三个区域的选择性剪接而产生：V (IIICS)、EIIIA (ED-A) 和 EIIIB (ED-B)。带有 EIIIA 和 EIIIB 片段的 FN 在胚胎发生过程中普遍存在，在正常成人组织中表达程度较低，并且可能在成人组织损伤部位局部重新表达。 RNase 图谱显示正常大鼠动脉表达低水平的 FN，主要是 EIIIA(-) 和 EIIIB(-)。球囊损伤后，动脉壁产生的 FN 转录物总水平增加，其中优先包括 EIIIA 和 EIIIB 片段。然而，尽管诱导总 FN mRNA 增加，球囊损伤不会改变 V120(-)、V95(+) 和 VO 剪接形式的相对组成。原位杂交显示，早在损伤后 4 天，内侧细胞就表达增加的总 FN mRNA，到 7 天，EIIIA(+)、EIIIB(+) 和 V120(+) FN 的新内膜和局部内侧细胞大量合成：巨噬细胞对观察到的血管 FN 合成没有显着贡献。与 mRNA 数据一致，免疫荧光显微镜分析显示受损动脉壁（尤其是新内膜内）EIIIB(+) 和 V+ FN 蛋白形式的沉积增加。我们的结果表明，特定 FN 亚型的局部合成对于球囊损伤后的新内膜形成很重要。
Fibronectins (FNs) comprise a family of adhesive extracellular matrix proteins that arise by alternative splicing in three regions: V (IIICS), EIIIA (ED-A), and EIIIB (ED-B). FNs bearing the EIIIA and EIIIB segments are prevalent during embryogenesis, expressed to lesser degrees in normal adult tissues, and may be locally reexpressed at sites of adult tissue injury. RNase mapping shows that normal rat arteries express low levels of FNs that are predominantly EIIIA(-) and EIIIB(-). Following balloon injury, arterial walls produce increased total levels of FN transcripts that preferentially include both the EIIIA and EIIIB segments. However, despite inducing increased total FN mRNA, balloon injury does not alter the relative composition of V120(-), V95(+), and VO spliced forms. In situ hybridization reveals that as early as 4 days after injury medial cells express increased total FN mRNA, and by 7 days substantial neointimal and focal medial synthesis of EIIIA(+), EIIIB(+), and V120(+) FNs occurs: macrophages do not significantly contribute to this observed vascular FN synthesis. Consistent with the mRNA data, immunofluorescence microscopic analysis reveals increased deposition of EIIIB(+) and V+ FN protein forms in injured arterial walls, particularly within the neointima. Our results suggest that local synthesis of specific FN isoforms is important to the neointimal formation that ensues after balloon injury.