Endothelial TRIM35‐Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts
Abstract Vascular calcification is a highly regulated process in cardiovascular disease (CVD) and is strongly correlated with morbidity and mortality, especially in the adverse stage of vascular remodeling after coronary artery bypass graft surgery (CABG). However, the pathogenesis of vascular graft...
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409641 |
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| author | Yiming Leng Wei Wang Jun Lu Jingyuan Chen Xuliang Chen Yalan Li Jie Wang Yuanyuan Liu Qian Tan Wenjing Yang Youxiang Jiang Peiyuan Huang Jingjing Cai Hong Yuan Liang Weng Qingbo Xu Yao Lu |
| author_facet | Yiming Leng Wei Wang Jun Lu Jingyuan Chen Xuliang Chen Yalan Li Jie Wang Yuanyuan Liu Qian Tan Wenjing Yang Youxiang Jiang Peiyuan Huang Jingjing Cai Hong Yuan Liang Weng Qingbo Xu Yao Lu |
| author_sort | Yiming Leng |
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| description | Abstract Vascular calcification is a highly regulated process in cardiovascular disease (CVD) and is strongly correlated with morbidity and mortality, especially in the adverse stage of vascular remodeling after coronary artery bypass graft surgery (CABG). However, the pathogenesis of vascular graft calcification, particularly the role of endothelial‐smooth muscle cell interaction, is still unclear. To test how ECs interact with SMCs in artery grafts, single‐cell analysis of wild‐type mice is first performed using an arterial isograft mouse model and found robust cytokine‐mediated signaling pathway activation and SMC proliferation, together with upregulated endothelial tripartite motif 35 (TRIM35) expression. Unexpectedly, severe SMC calcification in artery grafts is found in TRIM35 conditional endothelial knockout (cKO) mice. Calcified medium (comprising calcium chloride and beta‐glycerophosphate)‐induced calcium deposition in vitro is also found in SMCs cocultured with TRIM35 knockout endothelium. This extraordinary phenomenon is further confirmed to be induced by increased MMP10 secretion. Mechanistically, endothelial TRIM35 inhibits MMP10 expression and secretion by promoting K63‐linked ubiquitination of RelB and maintaining its nuclear localization, consequently inhibiting nuclear transcription of MMP10 through the noncanonical NF‐κB signaling pathway. Targeting MMP10 in situ in arterial isografts can effectively alleviate vascular calcification caused by conditional endothelial TRIM35 knockout. These findings demonstrated that TRIM35 inhibited vascular calcification during arterial isograft remodeling, a process that is driven by the aberrant secretion of endothelial MMP10. Targeting MMP10 pathway may be a potential therapeutic strategy for vascular calcification in vessel grafts. |
| format | Article |
| id | doaj-art-ae268502d0de407aa8a93477afdeb7b5 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-ae268502d0de407aa8a93477afdeb7b52025-08-20T02:24:47ZengWileyAdvanced Science2198-38442025-03-011211n/an/a10.1002/advs.202409641Endothelial TRIM35‐Regulated MMP10 Release Exacerbates Calcification of Vascular GraftsYiming Leng0Wei Wang1Jun Lu2Jingyuan Chen3Xuliang Chen4Yalan Li5Jie Wang6Yuanyuan Liu7Qian Tan8Wenjing Yang9Youxiang Jiang10Peiyuan Huang11Jingjing Cai12Hong Yuan13Liang Weng14Qingbo Xu15Yao Lu16Clinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaDepartment of Laboratory Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaDepartment of Cardiovascular Surgery Xiangya Hospital Central South University Changsha 410028 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaMRC Integrative Epidemiology Unit (IEU) Bristol Medical School University of Bristol Oakfield House, Oakfield Grove Bristol BS8 2BN UKClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaDepartment of Pathology School of Basic Medical Sciences Peking University Third Hospital Peking University Health Science Center Beijing 100083 P. R. ChinaDepartment of Cardiology, the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310058 P. R. ChinaClinical Research Center Postdoctoral Station of Clinical Medicine The Third Xiangya Hospital Central South University Changsha 410013 P. R. ChinaAbstract Vascular calcification is a highly regulated process in cardiovascular disease (CVD) and is strongly correlated with morbidity and mortality, especially in the adverse stage of vascular remodeling after coronary artery bypass graft surgery (CABG). However, the pathogenesis of vascular graft calcification, particularly the role of endothelial‐smooth muscle cell interaction, is still unclear. To test how ECs interact with SMCs in artery grafts, single‐cell analysis of wild‐type mice is first performed using an arterial isograft mouse model and found robust cytokine‐mediated signaling pathway activation and SMC proliferation, together with upregulated endothelial tripartite motif 35 (TRIM35) expression. Unexpectedly, severe SMC calcification in artery grafts is found in TRIM35 conditional endothelial knockout (cKO) mice. Calcified medium (comprising calcium chloride and beta‐glycerophosphate)‐induced calcium deposition in vitro is also found in SMCs cocultured with TRIM35 knockout endothelium. This extraordinary phenomenon is further confirmed to be induced by increased MMP10 secretion. Mechanistically, endothelial TRIM35 inhibits MMP10 expression and secretion by promoting K63‐linked ubiquitination of RelB and maintaining its nuclear localization, consequently inhibiting nuclear transcription of MMP10 through the noncanonical NF‐κB signaling pathway. Targeting MMP10 in situ in arterial isografts can effectively alleviate vascular calcification caused by conditional endothelial TRIM35 knockout. These findings demonstrated that TRIM35 inhibited vascular calcification during arterial isograft remodeling, a process that is driven by the aberrant secretion of endothelial MMP10. Targeting MMP10 pathway may be a potential therapeutic strategy for vascular calcification in vessel grafts.https://doi.org/10.1002/advs.202409641calcificationendothelial cellsMMP10smooth muscle cellsTRIM35 |
| spellingShingle | Yiming Leng Wei Wang Jun Lu Jingyuan Chen Xuliang Chen Yalan Li Jie Wang Yuanyuan Liu Qian Tan Wenjing Yang Youxiang Jiang Peiyuan Huang Jingjing Cai Hong Yuan Liang Weng Qingbo Xu Yao Lu Endothelial TRIM35‐Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts Advanced Science calcification endothelial cells MMP10 smooth muscle cells TRIM35 |
| title | Endothelial TRIM35‐Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts |
| title_full | Endothelial TRIM35‐Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts |
| title_fullStr | Endothelial TRIM35‐Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts |
| title_full_unstemmed | Endothelial TRIM35‐Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts |
| title_short | Endothelial TRIM35‐Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts |
| title_sort | endothelial trim35 regulated mmp10 release exacerbates calcification of vascular grafts |
| topic | calcification endothelial cells MMP10 smooth muscle cells TRIM35 |
| url | https://doi.org/10.1002/advs.202409641 |
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