Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle.
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.
Kivelä
Riikka
R
LIKES Research Center for Sport and Health Sciences, Rautpohjankatu 8a, Jyväskylä FIN-40740, Finland. riikka.kivela@likes.fi
Silvennoinen
Mika
M
Touvra
Anna-Maria
AM
Lehti
T Maarit
TM
Kainulainen
Heikki
H
Vihko
Veikko
V
D043925:Angiogenesis Inducing Agents; D000818:Animals; D002196:Capillaries / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000098:blood supply / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010805:Physical Conditioning, Animal; D012259:Ribonuclease, Pancreatic / Q000502:physiology*
D043925:Angiogenesis Inducing Agents; C046366:angiogenin; D012259:Ribonuclease, Pancreatic