Fiber capillary regression and endothelial cell apoptosis in the soleus muscle of hindlimb unloaded rats: role of angiogenic regulators

Abstract

The aim of present study was to determine the changes in the 3‐D architecture of the intramuscular endothelial networks and the responses of angiogenic and its inhibitory factors in atrophied soleus muscles. The hindlimbs of male Wistar rats were unloaded for 2 weeks by tail suspension. The endothelial network of soleus muscle was visualized by confocal microscopy. Apoptotic endothelial cells were identified by DNA fragmentation (TUNEL) using immunofluorescent staining. The mRNA levels of angiogenic factors (VEGF, KDR, Flt‐1, Ang‐1, Ang‐2, Tie‐2, HIF‐1 alpha) and inhibitory factors (TSP‐1 and caspase‐3) were determined by TaqMan probe‐based real‐time PCR. Chronic unloading resulted in a decrease in the number of anastomoses and tortuosity, appearance of TUNEL‐positive endothelial cells, a decrease in angiogenic factor mRNA, an increase in the Ang‐2‐to‐Ang‐1 ratio, and an increase in angiogenic inhibitor mRNA. The data suggest vasculature destabilization with chronic unloading and indicate that both a decrease in angiogenic factors and increase in angiogenic inhibitory factors play a role in this process.Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, no. 19300196.