Thermal Effect on Human Skeletal Muscle-derived Cell Transcriptomes: Possibility of Prevention against Atherosclerosis

Abstract

Aims: Our previous study demonstrated an increase in the serum adiponectin level and decrease in soluble urokinase-type plasminogen activator receptor (suPAR) after the application of thermal sheets to femoral skeletal muscle in healthy people. Based on these results, the possibility of atherosclerotic cardiovascular disease (ASCVD) prevention effect by thermal stimulation was considered. The present study examined the effect of thermal stimulation on the skeletal muscle-derived cell (SMDC) to determine the changes of ASCVD-related molecules and the mechanism of anti-atherogenic changes in serum adiponectin level and suPAR value. Study Design: Experimental study comparing transcriptome between cells cultured at higher temperature and control cells. Place and Duration of Study: From September 2015 to March 2017, Division of Physiology and Metabolism, University of Hyogo, Japan. Methodology: SMDC were cultured at 42°C and 37°C for 20 hours, and its gene expression was analysed using microarray technology. Results: Thermal stimulation to SMDC confirmed a significant increase in expression of 1,072 genes and significant inhibition in expression of 1,123 genes. Among these genes, multiple genes were factors affecting ASCVD. Furthermore, in gene ontology analysis and pathway analysis, factors considered to be related to ASCVD, such as lipid metabolism and glucose metabolism, were significantly included. Although thermal stimulation on SMDC induced changes in the gene expression of factors promoting ASCVD, changes in factors protecting against ASCVD were predominant. Besides, dipeptidyl peptidase IV (DPP-4) mRNA expression was decreased by thermal stimulation to SMDC. Despite the increase in serum adiponectin levels, the concentration of DPP-4 released in the medium was significantly higher in the cells exposed to thermal stimulation compared to control cells. Furthermore, any changes were not responsible for the decreased serum suPAR. Conclusion: These results suggest that thermal stimulation might change gene expression beneficial for ASCVD prevention in SMDC. Further study is needed to verify the ASCVD preventive effect by thermal stimulation in-vivo.