| First Author | Shimba Y | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 4077 |
| PubMed ID | 30858489 | Mgi Jnum | J:276942 |
| Mgi Id | MGI:6307441 | Doi | 10.1038/s41598-019-40643-1 |
| Citation | Shimba Y, et al. (2019) Skeletal Muscle-specific PGC-1alpha Overexpression Suppresses Atherosclerosis in Apolipoprotein E-Knockout Mice. Sci Rep 9(1):4077 |
| abstractText | Endurance exercise training prevents atherosclerosis. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) increases myokine secretion from the skeletal muscle, and these myokines have been shown to affect the function of multiple organs. Since endurance exercise training increases PGC-1alpha expression in skeletal muscles, we investigated whether skeletal muscle-specific PGC-1alpha overexpression suppresses atherosclerosis. Apolipoprotein E-knockout (ApoE-KO)/PGC-1alpha mice, which overexpress PGC-1alpha in the skeletal muscle of ApoE-KO mice, were sacrificed, and the atherosclerotic plaque area, spontaneous activity, plasma lipid profile, and aortic gene expression were measured. Immunohistochemical analyses were also performed. The atherosclerotic lesions in ApoE-KO/PGC-1alpha mice were 40% smaller than those in ApoE-KO mice, concomitant with the reduction in vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levels in the aorta. Spontaneous activity and plasma lipid profiles were not changed by the overexpression of PGC-1alpha in the skeletal muscle. In human umbilical vein endothelial cells, Irisin and beta-aminoisobutyric acid (BAIBA), PGC-1alpha-dependent myokines, inhibited the tumor necrosis factor alpha-induced VCAM-1 gene and protein expression. BAIBA also inhibited TNFalpha-induced MCP-1 gene expression. These results showed that the skeletal muscle-specific overexpression of PGC-1alpha suppresses atherosclerosis and that PGC-1alpha-dependent myokines may be involved in the preventive effects observed. |
