MMP9 Associates with Endothelial Glycocalyx Degradation During Haemorrhagic Fever with Renal Syndrome

• Introduction: Haemorrhagic fever with renal syndrome (HFRS) is characterized by fever, hypotension, vascular leakage, thrombocytopenia and renal failure. HFRS in Sweden is caused by the Puumala hantavirus and is spread by viral-infested droppings from bank voles. The health care system has little to offer these patients since there is no antiviral treatment and as of yet there is no vaccine prophylaxis available. We previously showed that a marker of endothelial glycocalyx degradation (Syndecan-1) was associated with disease severity and disseminated intravascular coagulation during HFRS (Connolly-Andersen et al., 2014, Open Forum Infect Dis.).Methods: We analysed the levels of other endothelial glycocalyx degradation markers (heparan sulfate, soluble thrombomodulin, albumin), a potential “sheddase”: Matrix Metalloproinase 9 (MMP9) and neutrophil activation/tissue damage (neutrophil gelatinase-associated lipocalin, NGAL) in patient plasma from 44 HFRS patients collected consecutively following disease onset. We used the generalized estimating equation to analyse the association between endothelial glycocalyx degradation, MMP9 levels, neutrophil activation/tissue damage and HFRS disease outcome (need for oxygen, transfusion with blood components, need for intensive care unit (ICU) treatment and renal damage).Results: 44 HFRS patients were included in this study (29 females (66%)); need for oxygen: 11 (25%); transfusion with blood components: 3 (7%) and stay at ICU: 2 (5%)). The levels of MMP9 were significantly associated with all markers of endothelial glycocalyx degradation. Neutrophil activation/tissue damage (NGAL) was also significantly associated with MMP9 and endothelial glycocalyx degradation markers (apart from albumin (p = 0.053). In addition degradation of endothelial glycocalyx associated with HFRS disease outcome.Conclusion: Degradation of the endothelial glycocalyx could be a potential mechanism of HFRS pathogenesis, and potentially MMP9 could contribute to degradation of the endothelial glycocalyx

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

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