Morphological and biochemical changes of lymphatic vessels in the soleus muscle of mice after hindlimb unloading

• Published in: Muscle & nerve Vol. 64; no. 5; pp. 620 - 628
• Main Authors: Kawashima, Takafumi, Ji, Rui‐Cheng, Itoh, Yuta, Agata, Nobuhide, Sasai, Nobuaki, Murakami, Taro, Sokabe, Masahiro, Hamada, Fumihiko, Kawakami, Keisuke
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.11.2021; Wiley Subscription Services, Inc
• Subjects: Animals; Atrophy; Blood; Blood vessels; Capillaries; Energy metabolism; Growth factors; Hindlimb; Hindlimb Suspension; lymphangiogenic factor; Lymphatic system; lymphatic vessel; Lymphatic Vessels; Male; Metabolic wastes; Mice; Mice, Inbred C57BL; Muscle, Skeletal - pathology; Muscles; Muscular Atrophy - pathology; Polymerase chain reaction; Skeletal muscle; Soleus muscle; tail suspension; Tissues; Transcription; Unloading; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Western blotting; atrophy; lymphatic vessel; tail suspension; skeletal muscle; lymphangiogenic factor
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.27402

Introduction/Aims Lymphatic vessels are responsible for the removal of metabolic waste from body tissues. They also play a crucial role in skeletal muscle functioning thorough their high‐energy metabolism. In this study we investigated whether disuse muscle atrophy induced by hindlimb unloading is associated with an alteration in the number of lymphatic vessels and differential expression of lymphangiogenic factors in the soleus muscle. Methods Male C57BL/6 mice were subjected to tail suspension (TS) for 2 or 4 weeks to induce soleus muscle atrophy. After TS, lymphatic and blood capillaries in the soleus muscle were visualized and counted by double staining with LYVE‐1 and CD31. The protein and mRNA levels of vascular endothelial growth factor (VEGF)‐C, VEGF‐D, and vascular endothelial growth factor receptor‐3 were measured by Western blotting and real‐time reverse transcript polymerase chain reaction, respectively. Results TS for 2 weeks resulted in a significant decrease in the number of blood capillaries compared with controls. However, there was no significant change in the number of lymphatic capillaries. By contrast, TS for 4 weeks resulted in a significant decrease in the number of lymphatic and blood capillaries. We observed a significant decrease in the mRNA levels of VEGF‐C and VEGF‐D in mice subjected to TS for 4 weeks. Discussion The decrease of intramuscular lymphatic vessels may a crucial role in the process of muscle atrophy.