SIRT 1‐mediated epigenetic downregulation of plasminogen activator inhibitor‐1 prevents vascular endothelial replicative senescence
| Autor: | Hou-Zao Chen, Yong-Jun Li, De-Long Hao, Peng Gao, Li-Shan Lian, De-Pei Liu, Shuang Zhou, Yan-Zhen Wan, Zhu-Qin Zhang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Senescence Aging endothelial replicative senescence PAI-1 Down-Regulation Mice Transgenic Biology Umbilical vein Epigenesis Genetic Histone H4 Mice chemistry.chemical_compound SIRT1 Sirtuin 1 Plasminogen Activator Inhibitor 1 Serpin E2 Human Umbilical Vein Endothelial Cells Animals Humans Cellular Senescence H4K16 acetylation Original Articles Cell Biology Molecular biology Plaque Atherosclerotic Cell biology chemistry Plasminogen activator inhibitor-1 biology.protein Histone deacetylase atherosclerosis Plasminogen activator Cell aging epigenetic |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9726 1474-9718 |
| Popis: | The inactivation of plasminogen activator inhibitor-1 (PAI-1) has been shown to exert beneficial effects in age-related vascular diseases. Limited information is available on the molecular mechanisms regarding the negatively regulated expression of PAI-1 in the vascular system. In this study, we observed an inverse correlation between SIRT1, a class III histone deacetylase, and PAI-1 expression in human atherosclerotic plaques and the aortas of old mice, suggesting that internal negative regulation exists between SIRT1 and PAI-1. SIRT1 overexpression reversed the increased PAI-1 expression in senescent human umbilical vein endothelial cells (HUVECs) and aortas of old mice, accompanied by decreased SA-β-gal activity in vitro and improved endothelial function and reduced arterial stiffness in vivo. Moreover, the SIRT1-mediated inhibition of PAI-1 expression exerted an antisenescence effect in HUVECs. Furthermore, we demonstrated that SIRT1 is able to bind to the PAI-1 promoter, resulting in a decrease in the acetylation of histone H4 lysine 16 (H4K16) on the PAI-1 promoter region. Thus, our findings suggest that the SIRT1-mediated epigenetic inhibition of PAI-1 expression exerts a protective effect in vascular endothelial senescence. |
| Databáze: | OpenAIRE |
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