Original investigation

Exercise-induced expression of angiogenic growth factors in skeletal muscle and in capillaries of healthy and diabetic mice

Riikka Kivelä^1,2 , Mika Silvennoinen^1,2 , Maarit Lehti¹ , Sanni Jalava³ , Veikko Vihko¹ and Heikki Kainulainen^1,2

¹LIKES Research Center for Sport and Health Sciences, Rautpohjankatu 8a, 40700 Jyväskylä, Finland

²Neuromuscular Research Center, Department of Biology of Physical Activity, P.O. Box 35, 40014 University of Jyväskylä, Finland

³Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland

author email corresponding author email

Cardiovascular Diabetology 2008, 7:13doi:10.1186/1475-2840-7-13

Published:	1 May 2008

Abstract

Background

Diabetes has negative, and exercise training positive, effects on the skeletal muscle vasculature, but the mechanisms are not yet fully understood. In the present experiment the effects of running exercise on the mRNA expression of pro- and antiangiogenic factors were studied in healthy and diabetic skeletal muscle. The responses in capillaries and muscle fibers, collected from the muscle with laser capture microdissection, were also studied separately.

Methods

Healthy and streptozotocin-induced diabetic mice were divided into sedentary and exercise groups. Exercise was a single bout of 1 h running on a treadmill. Gastrocnemius muscles were harvested 3 h and 6 h post exercise, and angiogenesis-related gene expressions were analyzed with real-time PCR. In addition to muscle homogenates, capillaries and muscle fibers were collected from the muscle with laser capture microdissection method and analyzed for vascular endothelial growth factor-A (VEGF-A) and thrombospondin-1 (TSP-1) mRNA expression.

Results

Of the proangiogenic factors, VEGF-A and VEGF receptor-2 (VEGFR-2) mRNA expression increased significantly (P < 0.05) in healthy skeletal muscle 6 h post exercise. VEGF-B also showed a similar trend (P = 0.08). No significant change was observed post exercise in diabetic muscles in the expression of VEGF-A, VEGFR-2 or VEGF-B. The expression of angiogenesis inhibitor TSP-1 and angiogenic extracellular matrix protein Cyr61 were significantly increased in diabetic muscles (P < 0.05–0.01). Capillary mRNA expression resembled that in the muscle homogenates, however, the responses were greater in capillaries compared to muscle homogenates and pure muscle fibers.

Conclusion

The present study is the first to report the effects of a single bout of exercise on the expression of pro- and antiangiogenic factors in diabetic skeletal muscle, and it provides novel data about the separate responses in capillaries and muscle fibers to exercise and diabetes. Diabetic mice seem to have lower angiogenic responses to exercise compared to healthy mice, and they show markedly increased expression of angiogenesis inhibitor TSP-1. Furthermore, exercise-induced VEGF-A expression was shown to be greater in capillaries than in muscle fibers.