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首页> 外文期刊>Life sciences >Differential analyses of angiogenesis and expression of growth factors in micro- and macrovascular endothelial cells of type 2 diabetic rats.
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Differential analyses of angiogenesis and expression of growth factors in micro- and macrovascular endothelial cells of type 2 diabetic rats.

机译：2型糖尿病大鼠微血管和大血管内皮细胞中血管生成和生长因子表达的差异分析。

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AIMS: This study observed the relationship of angiogenesis and differential expression of growth factors and their receptors in micro- and macrovascular endothelial cells of diabetic and normal rats. MAIN METHODS: Myocardial microvascular endothelial cells (MMVEC) and aortic endothelial cells (AEC) were isolated from type 2 diabetic-Goto-Kakizaki (GK) rats and age-matched normal Wistar rats. In vitro and in vivo Angiogenesis assay were used to observe the difference between GK rats and Wistar rats. mRNA and protein expression were analyzed by Real-time RT-PCR and Western blotting. KEY FINDINGS: MMVEC but not AEC of diabetic rats had reduced abilities of angiogenesis in vitro. Real-time RT-PCR showed increased mRNA levels of VEGF, fms-like tyrosine kinase (Flt-1) and kinase insert domain containing receptor (Flk-1) in GK-MMVEC, but not the hypoxia-inducible factor-1alpha (Hif-1alpha), basic fibroblast growth factor (bFGF), fibroblast growth factor receptor 1 (FGFR1), Angiopoietin-1(Ang-1), Angiopoietin-2(Ang-2), Tie-1 and Tie-2. In contrast, Western blotting showed decreased protein levels of VEGF and receptors, including the phosphorylation of receptors. No significant differences in the expression of theses genes were observed between AEC from diabetic and control rats. Anti-rat VEGF antibodies inhibited MMVEC angiogenic function including cell proliferation, adhesion, migration, scratch wound healing and capillary-like tube formation. The in vivo angiogenesis assay had similar results. SIGNIFICANCE: These result indicated that decreased expression of VEGF and its receptors caused by post-transcription disorder in MMVEC may be responsible for diabetic impaired cardiac angiogenesis.
机译：目的：本研究观察了糖尿病和正常大鼠微血管和大血管内皮细胞中血管生成与生长因子及其受体差异表达的关系。主要方法：从2型糖尿病-Goto-Kakizaki（GK）大鼠和年龄匹配的正常Wistar大鼠中分离出心肌微血管内皮细胞（MMVEC）和主动脉内皮细胞（AEC）。体外和体内血管生成试验用于观察GK大鼠和Wistar大鼠之间的差异。通过实时RT-PCR和Western印迹分析mRNA和蛋白质表达。关键发现：糖尿病大鼠的MMVEC而非AEC在体外具有降低的血管生成能力。实时RT-PCR显示GK-MMVEC中VEGF，fms样酪氨酸激酶（Flt-1）和含激酶插入结构域的受体（Flk-1）的mRNA水平升高，但缺氧诱导因子1α（Hif -1alpha），碱性成纤维细胞生长因子（bFGF），成纤维细胞生长因子受体1（FGFR1），血管生成素-1（Ang-1），血管生成素2（Ang-2），Tie-1和Tie-2。相反，蛋白质印迹显示VEGF和受体的蛋白质水平降低，包括受体的磷酸化。在糖尿病和对照大鼠的AEC之间未观察到这些基因表达的显着差异。抗大鼠VEGF抗体抑制MMVEC血管生成功能，包括细胞增殖，粘附，迁移，刮擦伤口愈合和毛细血管样管形成。体内血管生成测定具有相似的结果。意义：这些结果表明，MMVEC中转录后疾病引起的VEGF及其受体表达降低可能是糖尿病性心脏血管生成受损的原因。

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