PKR deficiency delays vascular aging via inhibiting GSDMD-mediated endothelial cell hyperactivation
Summary: Vascular aging is an independent risk factor for cardiovascular diseases, but the regulatory mechanism is not clearly understood. In this study, we found that endothelial PKR activity is elevated in aging aorta tissues, which is accompanied with increased endothelial cell hyperactivation, I...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222021824 |
| _version_ | 1797946148479041536 |
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| author | Zhouyangfan Peng Xiqing Tan Liangpeng Xie Ze Li Sufang Zhou Yapei Li |
| author_facet | Zhouyangfan Peng Xiqing Tan Liangpeng Xie Ze Li Sufang Zhou Yapei Li |
| author_sort | Zhouyangfan Peng |
| collection | DOAJ |
| description | Summary: Vascular aging is an independent risk factor for cardiovascular diseases, but the regulatory mechanism is not clearly understood. In this study, we found that endothelial PKR activity is elevated in aging aorta tissues, which is accompanied with increased endothelial cell hyperactivation, IL-1β and HMGB1 release and vascular smooth muscle cell (VSMC) phenotype transforming. Global knockout of PKR exhibits significantly delayed vascular aging compared to wild-type mice at the same age. In vitro, using PKR siRNA or the cell hyperactivation inhibitor glycine or disulfiram can effectively inhibit H2O2 or palmitic acid-induced endothelial cell hyperactivation, IL-1β and HMGB1 release and co-cultured VSMC phenotype transforming. These results demonstrate that endothelial PKR activation induces GSDMD-mediated endothelial cell hyperactivation to release HMGB1 and IL-1β, which promotes the phenotype transforming of VSMC and subsequent accelerates the process of vascular aging. These discoveries will help to explore the new drug target to inhibit vascular aging. |
| first_indexed | 2024-04-10T21:06:22Z |
| format | Article |
| id | doaj.art-4eed84dc0e7b4b83880d492b0a9b0711 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T21:06:22Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-4eed84dc0e7b4b83880d492b0a9b07112023-01-22T04:41:50ZengElsevieriScience2589-00422023-01-01261105909PKR deficiency delays vascular aging via inhibiting GSDMD-mediated endothelial cell hyperactivationZhouyangfan Peng0Xiqing Tan1Liangpeng Xie2Ze Li3Sufang Zhou4Yapei Li5Department of Health Management Center, the Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of General Practice, the Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Hematology and Critical Care Medicine, the Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Hematology and Critical Care Medicine, the Third Xiangya Hospital, Central South University, Changsha, ChinaSchool of Basic Medical Sciences, Guangxi Medical University, Nanning, ChinaDepartment of Health Management Center, the Third Xiangya Hospital, Central South University, Changsha, China; Corresponding authorSummary: Vascular aging is an independent risk factor for cardiovascular diseases, but the regulatory mechanism is not clearly understood. In this study, we found that endothelial PKR activity is elevated in aging aorta tissues, which is accompanied with increased endothelial cell hyperactivation, IL-1β and HMGB1 release and vascular smooth muscle cell (VSMC) phenotype transforming. Global knockout of PKR exhibits significantly delayed vascular aging compared to wild-type mice at the same age. In vitro, using PKR siRNA or the cell hyperactivation inhibitor glycine or disulfiram can effectively inhibit H2O2 or palmitic acid-induced endothelial cell hyperactivation, IL-1β and HMGB1 release and co-cultured VSMC phenotype transforming. These results demonstrate that endothelial PKR activation induces GSDMD-mediated endothelial cell hyperactivation to release HMGB1 and IL-1β, which promotes the phenotype transforming of VSMC and subsequent accelerates the process of vascular aging. These discoveries will help to explore the new drug target to inhibit vascular aging.http://www.sciencedirect.com/science/article/pii/S2589004222021824Biological sciencesPhysiologyCellular physiologyCell biology |
| spellingShingle | Zhouyangfan Peng Xiqing Tan Liangpeng Xie Ze Li Sufang Zhou Yapei Li PKR deficiency delays vascular aging via inhibiting GSDMD-mediated endothelial cell hyperactivation iScience Biological sciences Physiology Cellular physiology Cell biology |
| title | PKR deficiency delays vascular aging via inhibiting GSDMD-mediated endothelial cell hyperactivation |
| title_full | PKR deficiency delays vascular aging via inhibiting GSDMD-mediated endothelial cell hyperactivation |
| title_fullStr | PKR deficiency delays vascular aging via inhibiting GSDMD-mediated endothelial cell hyperactivation |
| title_full_unstemmed | PKR deficiency delays vascular aging via inhibiting GSDMD-mediated endothelial cell hyperactivation |
| title_short | PKR deficiency delays vascular aging via inhibiting GSDMD-mediated endothelial cell hyperactivation |
| title_sort | pkr deficiency delays vascular aging via inhibiting gsdmd mediated endothelial cell hyperactivation |
| topic | Biological sciences Physiology Cellular physiology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222021824 |
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