Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle
Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle
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DOI：
10.1096/fj.05-4780fje
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发表时间：
2006-07-01
期刊：
影响因子：
4.8
通讯作者：
Vihko, Veikko
中科院分区：
文献类型：
--
作者：
Kivela, Riikka;Silvennoinen, Mika;Vihko, Veikko
糖尿病改变微血管结构和功能，是心血管疾病的主要危险因素。在糖尿病骨骼肌中，已经观察到血管生成受损和VEGF-A表达减少，而在健康肌肉中，已知运动具有相反的效果。我们研究了1型糖尿病和联合运动训练对小鼠骨骼肌血管生成mRNA表达和毛细血管化的影响。微阵列和实时PCR分析表明，糖尿病改变了参与血管生成的几个基因的表达。例如，促血管生成VEGF-A、VEGF-B、神经纤毛蛋白-1、VEGFR-1和VEGFR-2的水平降低，而抗血管生成血小板反应蛋白-1和视网膜母细胞瘤样-2的水平升高。运动训练缓解了其中一些变化，但不能完全恢复它们。VEGF-A蛋白质含量在糖尿病肌肉中也减少。与VEGF-A和其他血管生成因子水平降低以及血管生成抑制剂水平升高一致，与健康对照组相比，糖尿病小鼠的毛细血管与肌纤维比率较低。运动训练不能恢复糖尿病小鼠的毛细血管化。总之，这些数据表明，1型糖尿病与骨骼肌毛细血管化减少和复杂的血管生成途径的失调有关。
Diabetes alters microvascular structure and function and is a major risk factor for cardiovascular diseases. In diabetic skeletal muscle, impaired angiogenesis and reduced VEGF-A expression have been observed, whereas in healthy muscle exercise is known to have opposite effects. We studied the effects of type 1 diabetes and combined exercise training on angiogenic mRNA expression and capillarization in mouse skeletal muscle. Microarray and real-time PCR analyses showed that diabetes altered the expression of several genes involved in angiogenesis. For example, levels of proangiogenic VEGF-A, VEGF-B, neuropilin-1, VEGFR-1, and VEGFR-2 were reduced and the levels of antiangiogenic thrombospondin-1 and retinoblastoma like-2 were increased. Exercise training alleviated some of these changes, but could not completely restore them. VEGF-A protein content was also reduced in diabetic muscles. In line with the reduced levels of VEGF-A and other angiogenic factors, and increased levels of angiogenesis inhibitors, capillary-to-muscle fiber ratio was lower in diabetic mice compared to healthy controls. Exercise training could not restore capillarization in diabetic mice. In conclusion, these data illustrate that type 1 diabetes is associated with reduced skeletal muscle capillarization and the dysregulation of complex angiogenesis pathways.