Skeletal muscle-specific forkhead box protein-O1 overexpression suppresses atherosclerosis progression in apolipoprotein E-knockout mice
| Autor: | Rena Senda, Keigo Katayama, Akihito Morita, Yuki Shimba, Shinji Miura, Yasutomi Kamei, Masahiko Ikeda |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Apolipoprotein E medicine.medical_specialty Apolipoprotein B Calorie restriction Biophysics Vascular Cell Adhesion Molecule-1 FOXO1 Biochemistry Mice 03 medical and health sciences Apolipoproteins E 0302 clinical medicine Downregulation and upregulation Internal medicine Human Umbilical Vein Endothelial Cells medicine Animals Humans Muscle Skeletal Molecular Biology Mice Knockout biology Forkhead Box Protein O1 Tumor Necrosis Factor-alpha Chemistry Macrophages Skeletal muscle Cell Biology Atherosclerosis Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure 030220 oncology & carcinogenesis embryonic structures Knockout mouse Disease Progression biology.protein Tumor necrosis factor alpha |
| Zdroj: | Biochemical and Biophysical Research Communications. 540:61-66 |
| ISSN: | 0006-291X |
| Popis: | Calorie restriction (CR) reportedly prevents atherosclerotic diseases. Furthermore, CR induces forkhead box protein-O1 (FOXO-1) expression in the skeletal muscle, altering the character of the skeletal muscle. We previously reported that the change in skeletal muscle character, induced by the overexpression of peroxisome proliferator-activated receptor γ coactivator-1α, suppresses atherosclerotic progression in an atherosclerotic apolipoprotein E-knockout (ApoE-KO) mouse model. Thus, we hypothesized that skeletal muscle alternation induced by FOXO-1 may also have an anti-atherosclerotic effect in ApoE-KO mice. In this study, we investigated whether skeletal muscle-specific FOXO-1 overexpression suppresses the progression of atherosclerosis in ApoE-KO mice. We generated ApoE-KO/FOXO-1 mice, in which an ApoE-KO mouse was crossbred with a mouse presenting skeletal muscle-specific FOXO-1 overexpression (FOXO-1Tg). The mice were sacrificed at 20 weeks of age, and atherosclerotic plaque area and protein expression in the plaque were measured. Additionally, we measured the tumor necrosis factor α (TNFα)- induced mRNA expression in human umbilical vein endothelial cells (HUVECs), using serum collected from the FOXO-1Tg mice. Accordingly, ApoE-KO/FOXO-1 mice showed a 65% reduced atherosclerotic plaque area when compared with the ApoE-KO mice, with concomitantly reduced vascular cell adhesion molecule-1 (VCAM-1) and macrophage infiltration. As compared to serum from wild-type mice, the serum collected from the FOXO-1Tg mice significantly suppressed the mRNA expression of VCAM-1, an atherosclerosis initiation factor, in TNFα-treated HUVECs. Therefore, these data suggest that skeletal muscle-specific FOXO-1 overexpression suppresses the progression of atherosclerosis in ApoE-KO mice. In part, the CR-induced anti-atherosclerotic effect could be attributed to FOXO-1 upregulation in the skeletal muscle. |
| Databáze: | OpenAIRE |
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