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Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle.

Authors: Kivela, R  Silvennoinen, M  Touvra, AM  Lehti, TM  Kainulainen, H  Vihko, V 
Citation: Kivela R, etal., FASEB J. 2006 Jul;20(9):1570-2.
Pubmed: (View Article at PubMed) PMID:16816123
DOI: Full-text: DOI:10.1096/fj.05-4780fje

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.

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CRRD Object Information
CRRD ID: 2313725
Created: 2009-10-12
Species: All species
Last Modified: 2009-10-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.