PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia
Abstract Neointimal hyperplasia occurs in the context of vascular injury, such as stent intervention or balloon angioplasty. However, the role of mechanical forces in this process remains to be studied. In this study, a rat carotid artery intimal injury model was established. RNA-sequencing and tran...
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2025-08-01
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| Series: | Cellular and Molecular Life Sciences |
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| Online Access: | https://doi.org/10.1007/s00018-025-05790-x |
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| author | Minwen Zou Kaichuang Ye Jing Yan Shoumin Zhang Han Bao Zhiyin Li Yuting Tao Xing Zhang Wenhao Tian Yingxin Qi Yunlong Huo Yue Han |
| author_facet | Minwen Zou Kaichuang Ye Jing Yan Shoumin Zhang Han Bao Zhiyin Li Yuting Tao Xing Zhang Wenhao Tian Yingxin Qi Yunlong Huo Yue Han |
| author_sort | Minwen Zou |
| collection | DOAJ |
| description | Abstract Neointimal hyperplasia occurs in the context of vascular injury, such as stent intervention or balloon angioplasty. However, the role of mechanical forces in this process remains to be studied. In this study, a rat carotid artery intimal injury model was established. RNA-sequencing and transmission electron microscopy revealed that intimal injury disrupted the balance of vascular energy metabolism and impaired the mitochondrial ultrastructure in vivo. The human carotid plaque and femoral artery plaque samples also exhibited alterations in mitochondrial morphology. Vascular smooth muscle cells (VSMCs) are the main components of neointimal hyperplasia and are subjected to cyclic stretch resulting from pulsatile pressure. In this study, we found that the application of cyclic stretch in vitro increased VSMC mitochondrial mass and function. In addition, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α) played an important role in regulating VSMC mitochondrial function in response to physiological stretch via the phosphorylation of Smad3. Increasing the activation of PGC1α by ZLN005 treatment effectively inhibited VSMC hyperproliferation after intimal injury in vivo. These results suggested that the regulation of PGC1α by p-Smad3 in response to physiological cyclic stretch may effectively alleviate neointimal hyperplasia by promoting mitochondrial function. PGC1α may be a potential therapeutic target for the prevention and treatment of neointimal hyperplasia. |
| format | Article |
| id | doaj-art-3ddbca124ece47c2b3dba6104d8ca06c |
| institution | DOAJ |
| issn | 1420-9071 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Springer |
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| series | Cellular and Molecular Life Sciences |
| spelling | doaj-art-3ddbca124ece47c2b3dba6104d8ca06c2025-08-20T03:04:35ZengSpringerCellular and Molecular Life Sciences1420-90712025-08-0182112110.1007/s00018-025-05790-xPGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasiaMinwen Zou0Kaichuang Ye1Jing Yan2Shoumin Zhang3Han Bao4Zhiyin Li5Yuting Tao6Xing Zhang7Wenhao Tian8Yingxin Qi9Yunlong Huo10Yue Han11Institute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityDepartment of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong UniversityAbstract Neointimal hyperplasia occurs in the context of vascular injury, such as stent intervention or balloon angioplasty. However, the role of mechanical forces in this process remains to be studied. In this study, a rat carotid artery intimal injury model was established. RNA-sequencing and transmission electron microscopy revealed that intimal injury disrupted the balance of vascular energy metabolism and impaired the mitochondrial ultrastructure in vivo. The human carotid plaque and femoral artery plaque samples also exhibited alterations in mitochondrial morphology. Vascular smooth muscle cells (VSMCs) are the main components of neointimal hyperplasia and are subjected to cyclic stretch resulting from pulsatile pressure. In this study, we found that the application of cyclic stretch in vitro increased VSMC mitochondrial mass and function. In addition, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α) played an important role in regulating VSMC mitochondrial function in response to physiological stretch via the phosphorylation of Smad3. Increasing the activation of PGC1α by ZLN005 treatment effectively inhibited VSMC hyperproliferation after intimal injury in vivo. These results suggested that the regulation of PGC1α by p-Smad3 in response to physiological cyclic stretch may effectively alleviate neointimal hyperplasia by promoting mitochondrial function. PGC1α may be a potential therapeutic target for the prevention and treatment of neointimal hyperplasia.https://doi.org/10.1007/s00018-025-05790-xVascular injuryVascular smooth muscle cellsCyclic stretchMitochondrial energy metabolismPGC1αMechanotransduction |
| spellingShingle | Minwen Zou Kaichuang Ye Jing Yan Shoumin Zhang Han Bao Zhiyin Li Yuting Tao Xing Zhang Wenhao Tian Yingxin Qi Yunlong Huo Yue Han PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia Cellular and Molecular Life Sciences Vascular injury Vascular smooth muscle cells Cyclic stretch Mitochondrial energy metabolism PGC1α Mechanotransduction |
| title | PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia |
| title_full | PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia |
| title_fullStr | PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia |
| title_full_unstemmed | PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia |
| title_short | PGC1α regulates the mitochondrial metabolism response to cyclic stretch, which inhibits neointimal hyperplasia |
| title_sort | pgc1α regulates the mitochondrial metabolism response to cyclic stretch which inhibits neointimal hyperplasia |
| topic | Vascular injury Vascular smooth muscle cells Cyclic stretch Mitochondrial energy metabolism PGC1α Mechanotransduction |
| url | https://doi.org/10.1007/s00018-025-05790-x |
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