Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection
Abstract Vasculitis and vascular injury are induced in coronavirus disease 2019 (COVID-19) patients, suggesting an association between multi-organ failure and sequelae. Vascular endothelial dysfunction induced by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) disrupts vascular...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-06569-7 |
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| author | Fumitaka Muramatsu Naoi Hosoe Tatsuya Suzuki Teppei Shimamura Yumiko Hayashi Kazuhiro Takara Lamri Lynda Anna Shimizu Weizhen Jia Yoshimi Noda Nobuyuki Takakura Toru Okamoto Hiroyasu Kidoya |
| author_facet | Fumitaka Muramatsu Naoi Hosoe Tatsuya Suzuki Teppei Shimamura Yumiko Hayashi Kazuhiro Takara Lamri Lynda Anna Shimizu Weizhen Jia Yoshimi Noda Nobuyuki Takakura Toru Okamoto Hiroyasu Kidoya |
| author_sort | Fumitaka Muramatsu |
| collection | DOAJ |
| description | Abstract Vasculitis and vascular injury are induced in coronavirus disease 2019 (COVID-19) patients, suggesting an association between multi-organ failure and sequelae. Vascular endothelial dysfunction induced by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) disrupts vascular barrier function, activates coagulation pathways, and induces extravasation of inflammatory cells. In addition to employing standard anti-inflammatory and antiviral agents, using treatments that stabilize and protect blood vessels following SARS-CoV-2 infection is a potentially effective strategy to relieve COVID-19 severity. Here, we focused on the vasoprotective effects of lysophosphatidic acid (LPA), a lipid mediator with diverse activities, and investigated whether it could be a novel therapeutic for COVID-19. Three-dimensional cultures of various human vascular endothelial cells that form luminal structures showed increased expression of LPA4 and entry receptors for SARS-CoV-2 infection, mimicking blood vessels in vivo. Validation using this culture system showed that LPA attenuated SARS-CoV-2 infection-induced vascular destruction and the activation of inflammatory signaling. In experiments with infected animals, LPA administration protected blood vessels and suppressed inflammation and vascular damage in lung tissue. The activation of LPA signaling in vascular endothelial cells may be an effective therapeutic approach for mitigating vascular injury in COVID-19. |
| format | Article |
| id | doaj-art-809abc317a114b2e8daad783d829b9b2 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-809abc317a114b2e8daad783d829b9b22025-08-20T03:05:23ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-06569-7Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infectionFumitaka Muramatsu0Naoi Hosoe1Tatsuya Suzuki2Teppei Shimamura3Yumiko Hayashi4Kazuhiro Takara5Lamri Lynda6Anna Shimizu7Weizhen Jia8Yoshimi Noda9Nobuyuki Takakura10Toru Okamoto11Hiroyasu Kidoya12Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Integrative Vascular Biology, Faculty of Medical Sciences, University of FukuiDepartment of Microbiology, Juntendo University School of MedicineDepartment of Computational and Systems Biology, Medical Research Institute, Institute of Science TokyoDepartment of Integrative Vascular Biology, Faculty of Medical Sciences, University of FukuiDepartment of Integrative Vascular Biology, Faculty of Medical Sciences, University of FukuiDepartment of Integrative Vascular Biology, Faculty of Medical Sciences, University of FukuiDepartment of Integrative Vascular Biology, Faculty of Medical Sciences, University of FukuiDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Microbiology, Juntendo University School of MedicineDepartment of Integrative Vascular Biology, Faculty of Medical Sciences, University of FukuiAbstract Vasculitis and vascular injury are induced in coronavirus disease 2019 (COVID-19) patients, suggesting an association between multi-organ failure and sequelae. Vascular endothelial dysfunction induced by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) disrupts vascular barrier function, activates coagulation pathways, and induces extravasation of inflammatory cells. In addition to employing standard anti-inflammatory and antiviral agents, using treatments that stabilize and protect blood vessels following SARS-CoV-2 infection is a potentially effective strategy to relieve COVID-19 severity. Here, we focused on the vasoprotective effects of lysophosphatidic acid (LPA), a lipid mediator with diverse activities, and investigated whether it could be a novel therapeutic for COVID-19. Three-dimensional cultures of various human vascular endothelial cells that form luminal structures showed increased expression of LPA4 and entry receptors for SARS-CoV-2 infection, mimicking blood vessels in vivo. Validation using this culture system showed that LPA attenuated SARS-CoV-2 infection-induced vascular destruction and the activation of inflammatory signaling. In experiments with infected animals, LPA administration protected blood vessels and suppressed inflammation and vascular damage in lung tissue. The activation of LPA signaling in vascular endothelial cells may be an effective therapeutic approach for mitigating vascular injury in COVID-19.https://doi.org/10.1038/s41598-025-06569-7Lysophosphatidic acid (LPA)COVID-19Vascular injuryVascular endothelial cellSARS-CoV-2 |
| spellingShingle | Fumitaka Muramatsu Naoi Hosoe Tatsuya Suzuki Teppei Shimamura Yumiko Hayashi Kazuhiro Takara Lamri Lynda Anna Shimizu Weizhen Jia Yoshimi Noda Nobuyuki Takakura Toru Okamoto Hiroyasu Kidoya Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection Scientific Reports Lysophosphatidic acid (LPA) COVID-19 Vascular injury Vascular endothelial cell SARS-CoV-2 |
| title | Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection |
| title_full | Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection |
| title_fullStr | Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection |
| title_full_unstemmed | Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection |
| title_short | Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection |
| title_sort | vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by sars cov 2 infection |
| topic | Lysophosphatidic acid (LPA) COVID-19 Vascular injury Vascular endothelial cell SARS-CoV-2 |
| url | https://doi.org/10.1038/s41598-025-06569-7 |
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