دورية أكاديمية
The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1
| العنوان: | The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1 |
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| المؤلفون: | Annika Schulz, Carolin C. Drost, Bettina Hesse, Katrin Beul, Göran R. Boeckel, Alexander Lukasz, Hermann Pavenstädt, Marcus Brand, Giovana S. Di Marco |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 6, p 5380 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | endothelial glycocalyx, soluble fms-like tyrosine kinase-1 (sFlt-1), heparin, endothelial dysfunction, endothelial injury, monocyte adhesion, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Soluble fms-like tyrosine kinase-1 (sFlt-1) is a secreted protein that binds heparan sulfate expressed on the endothelial glycocalyx (eGC). In this paper we analyze how excess sFlt-1 causes conformational changes in the eGC, leading to monocyte adhesion, a key event triggering vascular dysfunction. In vitro exposure of primary human umbilical vein endothelial cells to excess sFlt-1 decreased eGC height and increased stiffness as determined by atomic force microscopy (AFM). Yet, structural loss of the eGC components was not observed, as indicated by Ulex europaeus agglutinin I and wheat germ agglutinin staining. Moreover, the conformation observed under excess sFlt-1, a collapsed eGC, is flat and stiff with unchanged coverage and sustained content. Functionally, this conformation increased the endothelial adhesiveness to THP-1 monocytes by about 35%. Heparin blocked all these effects, but the vascular endothelial growth factor did not. In vivo administration of sFlt-1 in mice also resulted in the collapse of the eGC in isolated aorta analyzed ex vivo by AFM. Our findings show that excess sFlt-1 causes the collapse of the eGC and favors leukocyte adhesion. This study provides an additional mechanism of action by which sFlt-1 may cause endothelial dysfunction and injury. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/6/5380; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms24065380 |
| URL الوصول: | https://doaj.org/article/6310e2f4a45046febd011f9208bd7167 |
| رقم الأكسشن: | edsdoj.6310e2f4a45046febd011f9208bd7167 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms24065380 |