PCSK9 affects vascular senescence through the SIRT1 pathway
Age is an independent risk factor for atherosclerotic cardiovascular disease that increases the susceptibility of older adults to vascular intimal thickening, endothelial dysfunction, and thrombosis. However, the mechanism underlying vascular injury is not fully understood. In the present study, the...
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Elsevier
2025-03-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556525000294 |
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| author | Yuqin Wang Shaoqing Cao Zhangyu Wang Chengsi Li Jiangping Ye Yehong Liu Tianhui Jin Yuting Zhou Wentao Su Gangjun Zong |
| author_facet | Yuqin Wang Shaoqing Cao Zhangyu Wang Chengsi Li Jiangping Ye Yehong Liu Tianhui Jin Yuting Zhou Wentao Su Gangjun Zong |
| author_sort | Yuqin Wang |
| collection | DOAJ |
| description | Age is an independent risk factor for atherosclerotic cardiovascular disease that increases the susceptibility of older adults to vascular intimal thickening, endothelial dysfunction, and thrombosis. However, the mechanism underlying vascular injury is not fully understood. In the present study, the effect of proprotein convertase subtilin-type kexin 9 (PCSK9) inhibitors on the senescent state of human umbilical vein endothelial cells (HUVECs) and on senescent mice and lipopolysaccharides (LPS) were assessed. The senescent state of mice was delayed under PCSK9 inhibitor treatment, and the expression of P16, P21, and P53 proteins in senescent cells was increased because LPS induction stimulated PCSK9 activation. PCSK9 overexpression accelerated cell senescence, activated a large number of oxidative stress pathways, and increased the expression of senescence-related genes (including P16, P21, and P53). In addition, inhibition of the sirtuin 1 (SIRT)1 oxidative stress pathway can attenuate the aging-promoting effects of PCSK9, which are elevated as a result of LPS induction.The SIRT1 activator was more efficient than LPS alone in inducing the expression of senescence-related genes. Therefore, PCSK9 inhibitors can delay the aging of the vascular by reducing cellular SIRT1 levels. Therefore, it can be concluded that PCSK9 inhibition inhibits vascular senescence by reducing the expression of senescent proteins by regulating the SIRT1 pathway. |
| format | Article |
| id | doaj-art-3be40f4a7cc24d78916b485927571f23 |
| institution | Kabale University |
| issn | 1873-6815 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Experimental Gerontology |
| spelling | doaj-art-3be40f4a7cc24d78916b485927571f232025-02-11T04:33:30ZengElsevierExperimental Gerontology1873-68152025-03-01201112701PCSK9 affects vascular senescence through the SIRT1 pathwayYuqin Wang0Shaoqing Cao1Zhangyu Wang2Chengsi Li3Jiangping Ye4Yehong Liu5Tianhui Jin6Yuting Zhou7Wentao Su8Gangjun Zong9Department of Cardiovascular Medicine, Wuxi Clinical College, Anhui Medical University, Wuxi 214044, China; Department of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, ChinaDepartment of Cardiovascular Medicine, Wuxi Clinical College, Anhui Medical University, Wuxi 214044, China; Department of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, ChinaDepartment of Cardiovascular Medicine, Wuxi Clinical College, Anhui Medical University, Wuxi 214044, China; Department of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, ChinaDepartment of Cardiovascular Medicine, Wuxi Clinical College, Anhui Medical University, Wuxi 214044, China; Department of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, ChinaDepartment of Cardiovascular Medicine, Wuxi Clinical College, Anhui Medical University, Wuxi 214044, China; Department of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, ChinaDepartment of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, China; Department of Cardiovascular Medicine, 904th Hospital of the Joint Logistics Support Force of the People's Liberation Army, Wuxi 214044, ChinaDepartment of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, China; Department of Cardiovascular Medicine, 904th Hospital of the Joint Logistics Support Force of the People's Liberation Army, Wuxi 214044, ChinaDepartment of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, China; Department of Cardiovascular Medicine, 904th Hospital of the Joint Logistics Support Force of the People's Liberation Army, Wuxi 214044, ChinaDepartment of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, China; Department of Cardiovascular Medicine, 904th Hospital of the Joint Logistics Support Force of the People's Liberation Army, Wuxi 214044, ChinaDepartment of Cardiovascular Medicine, Wuxi Clinical College, Anhui Medical University, Wuxi 214044, China; Department of Cardiovascular Medicine, Fifth Clinical Medical College, Anhui Medical University, Anhui 230000, China; Department of Cardiovascular Medicine, 904th Hospital of the Joint Logistics Support Force of the People's Liberation Army, Wuxi 214044, China; Corresponding authors at: Department of Cardiology, No. 904 Hospital, Beidajie, Liangxi District, Wuxi City, Jiangsu Province, China.Age is an independent risk factor for atherosclerotic cardiovascular disease that increases the susceptibility of older adults to vascular intimal thickening, endothelial dysfunction, and thrombosis. However, the mechanism underlying vascular injury is not fully understood. In the present study, the effect of proprotein convertase subtilin-type kexin 9 (PCSK9) inhibitors on the senescent state of human umbilical vein endothelial cells (HUVECs) and on senescent mice and lipopolysaccharides (LPS) were assessed. The senescent state of mice was delayed under PCSK9 inhibitor treatment, and the expression of P16, P21, and P53 proteins in senescent cells was increased because LPS induction stimulated PCSK9 activation. PCSK9 overexpression accelerated cell senescence, activated a large number of oxidative stress pathways, and increased the expression of senescence-related genes (including P16, P21, and P53). In addition, inhibition of the sirtuin 1 (SIRT)1 oxidative stress pathway can attenuate the aging-promoting effects of PCSK9, which are elevated as a result of LPS induction.The SIRT1 activator was more efficient than LPS alone in inducing the expression of senescence-related genes. Therefore, PCSK9 inhibitors can delay the aging of the vascular by reducing cellular SIRT1 levels. Therefore, it can be concluded that PCSK9 inhibition inhibits vascular senescence by reducing the expression of senescent proteins by regulating the SIRT1 pathway.http://www.sciencedirect.com/science/article/pii/S0531556525000294Proprotein convertase subtilisin-type kexin 9Vascular senescenceLipopolysaccharidePlasmidSmall interfering RNA |
| spellingShingle | Yuqin Wang Shaoqing Cao Zhangyu Wang Chengsi Li Jiangping Ye Yehong Liu Tianhui Jin Yuting Zhou Wentao Su Gangjun Zong PCSK9 affects vascular senescence through the SIRT1 pathway Experimental Gerontology Proprotein convertase subtilisin-type kexin 9 Vascular senescence Lipopolysaccharide Plasmid Small interfering RNA |
| title | PCSK9 affects vascular senescence through the SIRT1 pathway |
| title_full | PCSK9 affects vascular senescence through the SIRT1 pathway |
| title_fullStr | PCSK9 affects vascular senescence through the SIRT1 pathway |
| title_full_unstemmed | PCSK9 affects vascular senescence through the SIRT1 pathway |
| title_short | PCSK9 affects vascular senescence through the SIRT1 pathway |
| title_sort | pcsk9 affects vascular senescence through the sirt1 pathway |
| topic | Proprotein convertase subtilisin-type kexin 9 Vascular senescence Lipopolysaccharide Plasmid Small interfering RNA |
| url | http://www.sciencedirect.com/science/article/pii/S0531556525000294 |
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