TY - JOUR
T1 - Matrix metalloproteinase-9 mediates endothelial glycocalyx degradation and correlates with severity of hemorrhagic fever with renal syndrome
AU - Jacquet, Chloé
AU - Gustafsson, Rasmus
AU - Patel, Ankit Kumar
AU - Hansson, Magnus
AU - Rankin, Gregory
AU - Bano, Fouzia
AU - Byström, Julia Wigren
AU - Blomberg, Anders
AU - Rasmuson, Johan
AU - Satchell, Simon
AU - Thunberg, Therese
AU - Ahlm, Clas
AU - Bally, Marta
AU - Fors Connolly, Anne-Marie
N1 - Publisher Copyright:
© 2025 The Author(s).
PY - 2025/9/19
Y1 - 2025/9/19
N2 - 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.
[See paper for graphical abstract]
AB - 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.
[See paper for graphical abstract]
U2 - 10.1016/j.isci.2025.113262
DO - 10.1016/j.isci.2025.113262
M3 - Article (Academic Journal)
C2 - 41054540
SN - 2589-0042
VL - 28
JO - iScience
JF - iScience
IS - 9
M1 - 113262
ER -