Lin T N, Wang C K, Cheung W M, Hsu C Y
Neuroscience Division, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
J Cereb Blood Flow Metab. 2000 Feb;20(2):387-95. doi: 10.1097/00004647-200002000-00021.
The angiopoietin/Tie receptor system may contribute to angiogenesis and vascular remodeling by mediating interactions of endothelial cells with smooth muscle cells and pericytes. The temporal expression of angiopoietin-1 (Angpo-1), angiopoietin-2 (Angpo-2), Tie-1, and Tie-2 mRNA was studied in a focal cerebral ischemia model in rats. The cDNA fragments obtained from reverse transcription polymerase chain reaction amplification were cloned and used as a probe to detect individual genes. Northern blot analysis showed a delayed increase of a 4.4-kb Angpo-1 transcript for up to 2 weeks after ischemia, eightfold higher than the values of the sham-operated controls. A biphasic expression of a 2.4-kb Angpo-2 transcript was noted, peaking at 24 hours (6.4-fold) and 2 weeks (4.6-fold) after ischemia. The expression of Tie-2 mRNA (4.3 kb), a receptor for Angpo-1, and Tie-1 mRNA (4.3 kb) also increased starting 24 hours after reperfusion and remained elevated for up to 2 weeks after ischemia. The temporal profiles of the expression of these genes were different from those of other angiogenic genes such as basic fibrobast growth factor/fibroblast growth factor receptor and vascular endothelial growth factor/vascular endothelial growth factor receptor and proteolytic enzymes (tissue-type plasminogen activator and urokinase plasminogen activator) and their inhibitors (plasminogen activator inhibitor-1). The expression patterns of these genes could be related to progressive tissue liquefaction and neovascularization after ischemia in this stroke model. Differential expression of these angiogenesis genes suggests the involvement of complex regulatory mechanisms that remain to be characterized.
血管生成素/Tie受体系统可能通过介导内皮细胞与平滑肌细胞和周细胞之间的相互作用，促进血管生成和血管重塑。在大鼠局灶性脑缺血模型中研究了血管生成素-1（Angpo-1）、血管生成素-2（Angpo-2）、Tie-1和Tie-2 mRNA的时间表达。从逆转录聚合酶链反应扩增获得的cDNA片段被克隆，并用作探针检测各个基因。Northern印迹分析显示，缺血后长达2周，4.4-kb的Angpo-1转录本延迟增加，比假手术对照组的值高8倍。观察到2.4-kb的Angpo-2转录本呈双相表达，在缺血后24小时（6.4倍）和2周（4.6倍）达到峰值。Angpo-1的受体Tie-2 mRNA（4.3 kb）和Tie-1 mRNA（4.3 kb）的表达也在再灌注后24小时开始增加，并在缺血后长达2周保持升高。这些基因表达的时间模式与其他血管生成基因不同，如碱性成纤维细胞生长因子/成纤维细胞生长因子受体、血管内皮生长因子/血管内皮生长因子受体以及蛋白水解酶（组织型纤溶酶原激活剂和尿激酶型纤溶酶原激活剂）及其抑制剂（纤溶酶原激活剂抑制剂-1）。在这个中风模型中，这些基因的表达模式可能与缺血后组织的渐进性液化和新血管形成有关。这些血管生成基因的差异表达表明存在有待表征的复杂调控机制。
