| First Author | Chen LD | Year | 2020 |
| Journal | Atherosclerosis | Volume | 297 |
| Pages | 64-73 | PubMed ID | 32078831 |
| Mgi Jnum | J:305463 | Mgi Id | MGI:6705812 |
| Doi | 10.1016/j.atherosclerosis.2020.01.017 | Citation | Chen LD, et al. (2020) T-cell death-associated gene 8 accelerates atherosclerosis by promoting vascular smooth muscle cell proliferation and migration. Atherosclerosis 297:64-73 |
| abstractText | BACKGROUND AND AIMS: Atherosclerosis is a serious cardiovascular disease, featuring inflammation, abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). During atherosclerosis, inflammation may cause low pH. T-cell death-associated gene 8 (Tdag8) is a proton-sensing receptor, however, the role of Tdag8 in VSMCs remains unknown. This study aimed to investigate the potential effects of Tdag8 in VSMCs during atherosclerosis. METHODS: We examined the expression of Tdag8 in an atherosclerotic model of high-fat-diet-fed ApoE(-/-) mice, while the role and mechanism of Tdag8 in phenotype transformation, proliferation and migration of VSMCs were investigated in a series of in vivo and in vitro experiments. RESULTS: We first found that Tdag8 expression at the mRNA and protein level was significantly increased in atherosclerotic ApoE(-/-) mice. Immunofluorescence staining showed that Tdag8 was primarily distributed in PCNA-positive VSMCs and the phenotype of VSMCs switching from contractile phenotype to synthetic phenotype. Additionally, the protein level of Tdag8 was upregulated in FBS-treated VSMCs. VSMCs proliferation and migration were inhibited by Tdag8 silencing and increased by Tdag8 overexpression. Further mechanistic studies showed that cAMP level was increased in Tdag8-overexpressing VSMCs and ApoE(-/-) mice. However, the PKA inhibitor H-89 reversed Tdag8-induced VSMC proliferation and migration. CONCLUSIONS: The results demonstrate that Tdag8 mediated phenotype transformation, proliferation and migration of VSMCs via the cAMP/PKA signaling pathway, thus partially contributing to atherosclerosis. |
