Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization
Differential expression of pro- and antiangiogenic factors in mouse strain-dependent hypoxia-induced retinal neovascularization
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DOI：
10.1038/labinvest.3700277
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发表时间：
2005-06-01
影响因子：
5
通讯作者：
Hinton, DR
中科院分区：
文献类型：
--
作者：
Chan, CK;Pham, LN;Hinton, DR
临床观察表明，遗传因素可能影响心血管疾病，增殖性糖尿病视网膜病变和肿瘤的血管生成反应的异质性。使用角膜微袋测定法在小鼠品系中进行的实验表明，血管生成的程度可以由遗传决定。在这里，我们建立了缺氧诱导的视网膜血管生成在多个小鼠品系中的品系依赖性，其与bFGF诱导的角膜血管生成的等级顺序一致。使用定量实时RT-PCR，分别测定缺氧0、6、12、24、48和96 h后，具有相对低和高水平血管生成的近交系C57 BL/6 J和129 S3/SvIM之间视网膜/脉络膜中血管内皮生长因子（VEGF）和血管生成素-2（Ang-2）的品系相关基因表达差异，缺氧诱导的血管生成配体，以及色素上皮衍生因子（PEDF）和血小板反应蛋白-1（TSP-1），内源性广谱抗血管生成因子。间接ELISA法检测VEGF和PEDF蛋白水平与mRNA表达的相关性。在缺氧开始时，与两种菌株中的Ang-2相比，PEDF和TSP-1水平均增加超过15倍，VEGF增加超过10倍。在新生血管形成开始时（48 h），血管生成更多的129 S3/SvIM株中VEGF和Ang-2 mRNA水平均升高（P
Clinical observations suggest that genetic factors may influence heterogeneity of angiogenic responses in cardiovascular disease, proliferative diabetic retinopathy, and neoplasia. Experiments among mouse strains using a corneal micropocket assay indicate that extent of angiogenesis may be genetically determined. Here, we established the strain-dependence of hypoxia-induced retinal angiogenesis in multiple mouse strains which paralleled the rank order found for bFGF-induced corneal angiogenesis. Using quantitative real-time RT-PCR, strain-related gene expression differences in retina/choroid between C57BL/6J and 129S3/SvIM, inbred strains with relatively low and high levels of angiogenesis, respectively, after 0, 6, 12, 24, 48, and 96 h hypoxia were determined for vascular endothelial growth factor ( VEGF) and angiopoietin-2 (Ang-2), angiogenic ligands potently induced by hypoxia, and for pigment epithelium-derived factor ( PEDF) and thrombospondin-1 (TSP-1), endogenous broad-spectrum antiangiogenic factors. Indirect ELISA was used to correlate VEGF and PEDF protein levels with mRNA expression. At the onset of hypoxia, both PEDF and TSP-1 levels were increased over 15-fold and VEGF was increased over 10-fold compared to Ang-2 in both strains. At the onset of neovascularization ( 48 h), both VEGF and Ang-2 mRNA levels were increased in the more angiogenic 129S3/SvIM strain (P