Characterization of thrombin receptor expression during vascular lesion formation.
Characterization of thrombin receptor expression during vascular lesion formation.
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血管病变形成过程中凝血酶受体表达的特征。
DOI：
10.1161/01.res.75.6.1029
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发表时间：
1994
影响因子：
20.1
通讯作者：
Salam,TA
中科院分区：
文献类型：
--
作者：
Wilcox,JN;Rodriguez,J;Subramanian,R;Ollerenshaw,J;Zhong,C;Hayzer,DJ;Horaist,C;Hanson,SR;Lumsden,A;Salam,TA
血管通过启动细胞增殖和迁移来响应损伤，从而导致血管病变形成。为了确定凝血酶和凝血酶受体在此过程中的作用，我们表征了正常和受损动脉中凝血酶受体的表达、凝血酶受体介导的平滑肌细胞有丝分裂以及体外凝血酶受体mRNA表达的调节。通过原位杂交，在正常大鼠或狒狒动脉中未检测到凝血酶受体 mRNA。使用抗凝血酶受体抗体（TR-R9）针对大鼠主动脉平滑肌细胞凝血酶受体的凝血酶裂解位点进行免疫组织化学分析，结果显示正常动脉内皮细胞和平滑肌细胞中凝血酶受体蛋白的染色水平较低。相反，球囊导管损伤在 6 小时内增加了内侧平滑肌细胞中凝血酶 mRNA 的表达。在整个血管病变形成过程中，这种增加的凝血酶受体表达在中膜和新内膜细胞中持续存在，主要是在细胞增殖活跃的区域。在体外，α-凝血酶以浓度依赖性方式刺激大鼠主动脉平滑肌细胞增殖。通过证明多克隆抗体 TR-R9 抑制凝血酶诱导的细胞增殖，证实了凝血酶受体激活是有丝分裂反应所必需的。在静置培养的大鼠主动脉平滑肌细胞中，碱性成纤维细胞生长因子（1 小时最大刺激 1.8 倍）和血小板衍生生长因子（8 小时和 24 小时最大刺激 2.4 倍）诱导凝血酶受体 mRNA 合成。总之，平滑肌细胞凝血酶受体表达的上调在血管损伤后很早就发生，并持续到整个新内膜发育过程。（摘要截短为 250 字）
Blood vessels respond to injury by initiating cell proliferation and migration that result in vascular lesion formation. To determine the roles of thrombin and the thrombin receptor in this process, we characterized thrombin receptor expression in normal and injured arteries, thrombin receptor-mediated smooth muscle cell mitogenesis, and the regulation of thrombin receptor mRNA expression in vitro. Thrombin receptor mRNA was not detected in normal rat or baboon arteries by in situ hybridization. Immunohistochemistry using an antithrombin receptor antibody (TR-R9), directed against the thrombin cleavage site of the rat aortic smooth muscle cell thrombin receptor, revealed low-level staining for thrombin receptor protein in endothelial cells and smooth muscle cells of normal arteries. In contrast, balloon catheter injury increased thrombin mRNA expression in medial smooth muscle cells within 6 hours. This increased thrombin receptor expression continued within the media and in neointimal cells throughout vascular lesion formation, predominantly in areas of active cell proliferation. In vitro, alpha-thrombin stimulates rat aortic smooth muscle cell proliferation in a concentration-dependent manner. That thrombin receptor activation is required for the mitogenic response was confirmed by demonstrating that the polyclonal antibody TR-R9 inhibits thrombin-induced cell proliferation. Thrombin receptor mRNA synthesis was induced by both basic fibroblast growth factor (maximal stimulation of 1.8-fold at 1 hour) and platelet-derived growth factor (maximal stimulation of 2.4-fold at 8 and 24 hours) in quiesced cultured rat aortic smooth muscle cells. In summary, upregulation of smooth muscle cell thrombin receptor expression occurs very early after vascular injury and continues throughout neointimal development.(ABSTRACT TRUNCATED AT 250 WORDS)