Matrix metalloproteinase-9 mediates endothelial glycocalyx degradation and correlates with severity of hemorrhagic fever with renal syndromeVisa övriga samt affilieringar
2025 (Engelska)Ingår i: iScience, E-ISSN 2589-0042, Vol. 28, nr 9, artikel-id 113262Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
Hemorrhagic fever with renal syndrome (HFRS) caused by Puumala virus (PUUV) leads to vascular dysfunction contributing to acute kidney injury (AKI) and pulmonary complications. The endothelial glycocalyx (eGLX) is crucial for vascular integrity, and its degradation may exacerbate disease severity. In this study, we examined the association between eGLX degradation and renal and pulmonary dysfunction in 44 patients with laboratory-confirmed PUUV infection. We measured plasma levels of eGLX degradation markers—syndecan-1, heparan sulfate, soluble thrombomodulin, and albumin—and found that these correlated with severe AKI and the need for oxygen therapy. In vitro experiments showed that matrix metalloproteinase-9 (MMP-9) and heparanase can degrade eGLX components, but albumin at physiological concentrations can mitigate this degradation and protect endothelial barrier function. These findings indicate that eGLX degradation contributes to HFRS pathogenesis and suggest that targeting the eGLX could be a therapeutic strategy to improve patient outcomes.
Ort, förlag, år, upplaga, sidor
Elsevier, 2025. Vol. 28, nr 9, artikel-id 113262
Nyckelord [en]
biochemistry, cell biology, microbiology
Nationell ämneskategori
Mikrobiologi inom det medicinska området Infektionsmedicin
Identifikatorer
URN: urn:nbn:se:umu:diva-243509DOI: 10.1016/j.isci.2025.113262ISI: 001562682200001Scopus ID: 2-s2.0-105013504540OAI: oai:DiVA.org:umu-243509DiVA, id: diva2:1996720
Forskningsfinansiär
Region Västerbotten, RV-836351Region Västerbotten, RV-967545Region Västerbotten, RV-939769Region Västerbotten, RV-967783Region Västerbotten, RV-982300Åke Wibergs Stiftelse, M18-0031Hjärt-Lungfonden, 20220179Kempestiftelserna, SMK21-00142025-09-102025-09-102025-09-10Bibliografiskt granskad