Capillary Remodeling and Inhibition of Angiogenic Growth Factors in Disused Skeletal Muscle

Abstract

The purpose of the present study was to investigate the changes of the anatomical pattern of capillarization of atrophied soleus muscles in rats. Additionally, we studied the relationship between muscle atrophy and angiogenic growth factors. Male Wistar rats were divided into hindlimb suspension rodent model (HS) and age-matched control groups. After 2 weeks of HS, the mean muscle fiber cross-sectional area and muscle mass were significantly decreased in HS compared to the control. Despite a higher capillary density, capillary-to-fiber ratio was significantly decreased in HS compared to the control. Decreased capillary-to-fiber ratio was significantly related to decreased succiniate dehydrogenase activities in HS. Furthermore, the vascular endothelial growth factor mRNA and protein decreased approximately 50% after HS. However, hypoxia-inducible factor-1 alfa mRNA levels of HS were not significantly altered. We found that HS produces a decrease in muscle capillarity. The down-regulation of VEGF gene expression is due to a negative feedback mechanism associated with lower metabolism activity and oxygen demand levels during HS.