Unveiling the protective role of ESM1 in endothelial cell proliferation and lipid reprogramming
Abstract Palmitic acid (PA), being the most prevalent free fatty acid in the human, holds significant implications as a risk factor for atherosclerosis (AS) due to its ability to induce physiological dysfunction in endothelial cells (ECs). Endothelial cell-specific molecule 1 (ESM1), has been identi...
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Nature Portfolio
2025-05-01
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| author | Yukun Li Anbo Gao Wenchao Zhou Xing Tang Tian Zeng Tingyu Fan Weimin Jiang Min Tang Fan Ouyang |
| author_facet | Yukun Li Anbo Gao Wenchao Zhou Xing Tang Tian Zeng Tingyu Fan Weimin Jiang Min Tang Fan Ouyang |
| author_sort | Yukun Li |
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| description | Abstract Palmitic acid (PA), being the most prevalent free fatty acid in the human, holds significant implications as a risk factor for atherosclerosis (AS) due to its ability to induce physiological dysfunction in endothelial cells (ECs). Endothelial cell-specific molecule 1 (ESM1), has been identified as a marker for activated ECs. Nevertheless, the mechanisms underlying ESM1-induced endothelial cell proliferation remain elusive. The expression of ESM1, ANGPTL4 and autophagy related protein were confirmed by western blot. Proliferation ability was tested by MTT and EdU. Lipids level was confirmed by Oil red staining. Autophagic flux was confirmed by Monodansylcadaverine (MDC) staining and pCMV-mCherry-GFP-LC3B fluorescence staining assay. The mouse model of AS was used to observe the effect of PA on the ESM1-ANGPTL4-autophagy signaling axis. This study elucidates ESM1-ANGPTL4 axis in maintaining proliferation of ECs and lipid reprogramming. Furthermore, it has been observed that PA has the ability to stimulate EC to autonomously increase the expression of ESM1, which in turn can counteract the detrimental effects of PA on ECs. Conversely, when ESM1 is suppressed, the damaging effects of PA on ECs are exacerbated. Mechanistically, our findings indicate that ESM1 facilitates EC proliferation and lipids homeostasis by up-regulating autophagy through ANGPTL4. This effect of ESM1 on ECs can be attenuated by ATG7 inhibiting. Additionally, the serum levels of ESM1 were found to be elevated in AS mice. ESM1 was found to enhance ECs proliferation and mitigate endothelial cell injury induced by PA through the upregulation of autophagy. This mechanism potentially serves as a protective factor against atherosclerosis progression. |
| format | Article |
| id | doaj-art-36e3f945b1fb4f2a94334f8882bc5f03 |
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| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-36e3f945b1fb4f2a94334f8882bc5f032025-08-20T02:55:38ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-00581-7Unveiling the protective role of ESM1 in endothelial cell proliferation and lipid reprogrammingYukun Li0Anbo Gao1Wenchao Zhou2Xing Tang3Tian Zeng4Tingyu Fan5Weimin Jiang6Min Tang7Fan Ouyang8Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South UniversityDepartment of Cardiology, Xiangya Hospital Zhuzhou, Zhuzhou Central Hospital, Central South University, Central South UniversityDepartment of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South UniversityDepartment of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South UniversityDepartment of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South UniversityDepartment of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South UniversityDepartment of Cardiology, Xiangya Hospital Zhuzhou, Zhuzhou Central Hospital, Central South University, Central South UniversityDepartment of Cardio-Thoracic Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Cardiology, Xiangya Hospital Zhuzhou, Zhuzhou Central Hospital, Central South University, Central South UniversityAbstract Palmitic acid (PA), being the most prevalent free fatty acid in the human, holds significant implications as a risk factor for atherosclerosis (AS) due to its ability to induce physiological dysfunction in endothelial cells (ECs). Endothelial cell-specific molecule 1 (ESM1), has been identified as a marker for activated ECs. Nevertheless, the mechanisms underlying ESM1-induced endothelial cell proliferation remain elusive. The expression of ESM1, ANGPTL4 and autophagy related protein were confirmed by western blot. Proliferation ability was tested by MTT and EdU. Lipids level was confirmed by Oil red staining. Autophagic flux was confirmed by Monodansylcadaverine (MDC) staining and pCMV-mCherry-GFP-LC3B fluorescence staining assay. The mouse model of AS was used to observe the effect of PA on the ESM1-ANGPTL4-autophagy signaling axis. This study elucidates ESM1-ANGPTL4 axis in maintaining proliferation of ECs and lipid reprogramming. Furthermore, it has been observed that PA has the ability to stimulate EC to autonomously increase the expression of ESM1, which in turn can counteract the detrimental effects of PA on ECs. Conversely, when ESM1 is suppressed, the damaging effects of PA on ECs are exacerbated. Mechanistically, our findings indicate that ESM1 facilitates EC proliferation and lipids homeostasis by up-regulating autophagy through ANGPTL4. This effect of ESM1 on ECs can be attenuated by ATG7 inhibiting. Additionally, the serum levels of ESM1 were found to be elevated in AS mice. ESM1 was found to enhance ECs proliferation and mitigate endothelial cell injury induced by PA through the upregulation of autophagy. This mechanism potentially serves as a protective factor against atherosclerosis progression.https://doi.org/10.1038/s41598-025-00581-7ESM1ANGPTL4Lipid metabolism reprogrammingEndothelial cell injuryAutophagyPalmitic acid |
| spellingShingle | Yukun Li Anbo Gao Wenchao Zhou Xing Tang Tian Zeng Tingyu Fan Weimin Jiang Min Tang Fan Ouyang Unveiling the protective role of ESM1 in endothelial cell proliferation and lipid reprogramming Scientific Reports ESM1 ANGPTL4 Lipid metabolism reprogramming Endothelial cell injury Autophagy Palmitic acid |
| title | Unveiling the protective role of ESM1 in endothelial cell proliferation and lipid reprogramming |
| title_full | Unveiling the protective role of ESM1 in endothelial cell proliferation and lipid reprogramming |
| title_fullStr | Unveiling the protective role of ESM1 in endothelial cell proliferation and lipid reprogramming |
| title_full_unstemmed | Unveiling the protective role of ESM1 in endothelial cell proliferation and lipid reprogramming |
| title_short | Unveiling the protective role of ESM1 in endothelial cell proliferation and lipid reprogramming |
| title_sort | unveiling the protective role of esm1 in endothelial cell proliferation and lipid reprogramming |
| topic | ESM1 ANGPTL4 Lipid metabolism reprogramming Endothelial cell injury Autophagy Palmitic acid |
| url | https://doi.org/10.1038/s41598-025-00581-7 |
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