Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia
Endothelial injury is a key factor initiating in-stent restenosis (ISR) following peripheral artery stent implantation. Genetically modified endothelial progenitor cells (EPCs) can promote reendothelialization of injured arteries and inhibit neointimal hyperplasia. However, the role of engineered EP...
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SAGE Publishing
2025-02-01
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| Series: | Journal of Tissue Engineering |
| Online Access: | https://doi.org/10.1177/20417314251315959 |
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| author | Yanchen Ye Lin Huang Kangjie Wang Yunhao Sun Zhihao Zhou Tang Deng Yunyan Liu Rui Wang Ridong Wu Chen Yao |
| author_facet | Yanchen Ye Lin Huang Kangjie Wang Yunhao Sun Zhihao Zhou Tang Deng Yunyan Liu Rui Wang Ridong Wu Chen Yao |
| author_sort | Yanchen Ye |
| collection | DOAJ |
| description | Endothelial injury is a key factor initiating in-stent restenosis (ISR) following peripheral artery stent implantation. Genetically modified endothelial progenitor cells (EPCs) can promote reendothelialization of injured arteries and inhibit neointimal hyperplasia. However, the role of engineered EPCs overexpressing lncRNA H19 in these processes remains unclear. We constructed EPCs overexpressing lncRNA H19 and investigated their effects and mechanisms in promoting reendothelialization and inhibiting neointimal hyperplasia both in vitro and in vivo . Compared to the normal control group, ISR patients exhibited a significant reduction in circulating EPCs. Engineered EPCs overexpressing lncRNA H19 promoted reendothelialization and inhibited neointimal hyperplasia in injured arteries. Exogenous overexpression of lncRNA H19 significantly upregulated the endothelial repair-related gene S1PR3 in EPCs, while the opposite was also observed. Additionally, engineered EPCs overexpressing S1PR3 promoted reendothelialization and inhibited neointimal hyperplasia in injured arteries. S1PR3 overexpression enhanced EPCs proliferation, migration, and tube formation in vitro ; these effects were lost with S1PR3 inhibition. Binding sites for H3K27 acetylation were identified on the S1PR3 promoter. Mechanistically, we found that lncRNA H19 directly interacted with HDAC2, a known H3K27ac deacetylase, disrupting its binding to H3K27 acetylation. Our findings suggest that lncRNA H19 positively regulates S1PR3 expression by disrupting HDAC2 / H3K27ac binding, thereby promoting reendothelialization of injured arteries and inhibiting neointimal hyperplasia. |
| format | Article |
| id | doaj-art-a2477ff7d1fd40c6a170a5901068f12f |
| institution | DOAJ |
| issn | 2041-7314 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Tissue Engineering |
| spelling | doaj-art-a2477ff7d1fd40c6a170a5901068f12f2025-08-20T03:12:58ZengSAGE PublishingJournal of Tissue Engineering2041-73142025-02-011610.1177/20417314251315959Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasiaYanchen Ye0Lin Huang1Kangjie Wang2Yunhao Sun3Zhihao Zhou4Tang Deng5Yunyan Liu6Rui Wang7Ridong Wu8Chen Yao9National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaInstitute of Interventional Radiology, Sun Yat-sen University, Zhuhai, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaEndothelial injury is a key factor initiating in-stent restenosis (ISR) following peripheral artery stent implantation. Genetically modified endothelial progenitor cells (EPCs) can promote reendothelialization of injured arteries and inhibit neointimal hyperplasia. However, the role of engineered EPCs overexpressing lncRNA H19 in these processes remains unclear. We constructed EPCs overexpressing lncRNA H19 and investigated their effects and mechanisms in promoting reendothelialization and inhibiting neointimal hyperplasia both in vitro and in vivo . Compared to the normal control group, ISR patients exhibited a significant reduction in circulating EPCs. Engineered EPCs overexpressing lncRNA H19 promoted reendothelialization and inhibited neointimal hyperplasia in injured arteries. Exogenous overexpression of lncRNA H19 significantly upregulated the endothelial repair-related gene S1PR3 in EPCs, while the opposite was also observed. Additionally, engineered EPCs overexpressing S1PR3 promoted reendothelialization and inhibited neointimal hyperplasia in injured arteries. S1PR3 overexpression enhanced EPCs proliferation, migration, and tube formation in vitro ; these effects were lost with S1PR3 inhibition. Binding sites for H3K27 acetylation were identified on the S1PR3 promoter. Mechanistically, we found that lncRNA H19 directly interacted with HDAC2, a known H3K27ac deacetylase, disrupting its binding to H3K27 acetylation. Our findings suggest that lncRNA H19 positively regulates S1PR3 expression by disrupting HDAC2 / H3K27ac binding, thereby promoting reendothelialization of injured arteries and inhibiting neointimal hyperplasia.https://doi.org/10.1177/20417314251315959 |
| spellingShingle | Yanchen Ye Lin Huang Kangjie Wang Yunhao Sun Zhihao Zhou Tang Deng Yunyan Liu Rui Wang Ridong Wu Chen Yao Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia Journal of Tissue Engineering |
| title | Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia |
| title_full | Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia |
| title_fullStr | Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia |
| title_full_unstemmed | Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia |
| title_short | Transplantation of engineered endothelial progenitor cells with H19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia |
| title_sort | transplantation of engineered endothelial progenitor cells with h19 overexpression promotes arterial reendothelialization and inhibits neointimal hyperplasia |
| url | https://doi.org/10.1177/20417314251315959 |
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