The Potential Impact of Heparanase Activity and Endothelial Damage in COVID-19 Disease

SARS-CoV-2 was first detected in 2019 in Wuhan, China. It has been found to be the most pathogenic virus among coronaviruses and is associated with endothelial damage resulting in respiratory failure. Determine whether heparanase and heparan sulfate fragments, biomarkers of endothelial function, can assist in the risk stratification and clinical management of critically ill COVID-19 patients admitted to the intensive care unit. We investigated 53 critically ill patients with severe COVID-19 admitted between March and April 2020 to the University Hospital RWTH Aachen. Heparanase activity and serum levels of both heparanase and heparan sulfate were measured on day one (day of diagnosis) and day three in patients with COVID-19. The patients were classified into four groups according to the severity of ARDS. When compared to baseline data (day one), heparanase activity increased and the heparan sulfate serum levels decreased with increasing severity of ARDS. The heparanase activity significantly correlated with the lactate concentration on day one (r = 0.34, p = 0.024) and on day three (r = 0.43, p = 0.006). Heparanase activity and heparan sulfate levels correlate with COVID-19 disease severity and outcome. Both biomarkers might be helpful in predicting clinical course and outcomes in COVID-19 patients

Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-in-Silico Approach Combining In Vitro Experiments and Machine Learning (vol 9, 393, 2018)

A Corrigendum on Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning by Zechendorf E, Vaßen P, Zhang J, Hallawa A, Martincuks A, Krenkel O, Müller-Newen G, Schuerholz T, Simon T-P, Marx G, Ascheid G, Schmeink A, Dartmann G, Thiemermann C and Martin L (2018). Front. Immunol. 9:393. doi: 10.3389/fimmu.2018.00393 In the original article, there was an error in the Author Contributions section. The wording used to declare the contribution of Elisabeth Zechendorf was not clear. The new Author Contributions section appears below. Conception and design: EZ, LM, GD, AS, and CT. In vitro experiments and data analyses: EZ, LM, TS, T-PS, AM, GM-N, OK, GM, and PV. Medical in silico experiments and data analyses: EZ, PV, JZ, GD, AS, LM, AH, and GA. EZ wrote the manuscript. Correction of the manuscript: EZ, PV, LM, CT, GM, GD, T-PS, and AS. All the authors reviewed and finally approved the manuscript. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Inhibition of Macrophage Migration Inhibitory Factor Activity Attenuates Haemorrhagic Shock-Induced Multiple Organ Dysfunction in Rats

OBJECTIVE: The aim of this study was to investigate (a) macrophage migration inhibitory factor (MIF) levels in polytrauma patients and rats after haemorrhagic shock (HS), (b) the potential of the MIF inhibitor ISO-1 to reduce multiple organ dysfunction syndrome (MODS) in acute (short-term and long-term follow-up) HS rat models and (c) whether treatment with ISO-1 attenuates NF-κB and NLRP3 activation in HS. BACKGROUND: The MODS caused by an excessive systemic inflammatory response following trauma is associated with a high morbidity and mortality. MIF is a pleiotropic cytokine which can modulate the inflammatory response, however, its role in trauma is unknown. METHODS: The MIF levels in plasma of polytrauma patients and serum of rats with HS were measured by ELISA. Acute HS rat models were performed to determine the influence of ISO-1 on MODS. The activation of NF-κB and NLRP3 pathways were analysed by western blot in the kidney and liver. RESULTS: We demonstrated that (a) MIF levels are increased in polytrauma patients on arrival to the emergency room and in rats after HS, (b) HS caused organ injury and/or dysfunction and hypotension (post-resuscitation) in rats, while (c) treatment of HS-rats with ISO-1 attenuated the organ injury and dysfunction in acute HS models and (d) reduced the activation of NF-κB and NLRP3 pathways in the kidney and liver. CONCLUSION: Our results point to a role of MIF in the pathophysiology of trauma-induced organ injury and dysfunction and indicate that MIF inhibitors may be used as a potential therapeutic approach for MODS after trauma and/or haemorrhage

Ribonuclease 1 attenuates septic cardiomyopathy and cardiac apoptosis in a murine model of polymicrobial sepsis.

Septic cardiomyopathy is a life-threatening organ dysfunction caused by sepsis. Ribonuclease 1 (RNase 1) belongs to a group of host-defense peptides that specifically cleave extracellular RNA (eRNA). The activity of RNase1 is inhibited by ribonuclease-inhibitor 1 (RNH1). The role of RNase 1 in septic cardiomyopathy and associated cardiac apoptosis, however, is completely unknown. Here, we showed that sepsis resulted in a significant increase in RNH1 and eRNA serum levels compared to those of healthy subjects (p < 0.05). Treatment with RNase 1 resulted in a significant decrease of apoptosis, induced by the intrinsic pathway, and TNF expression in murine cardiomyocytes exposed to either necrotic cardiomyocytes or serum of septic patients for 16 h (p < 0.05). Furthermore, treatment of septic mice with RNase 1 resulted in a reduction in cardiac apoptosis, TNF expression and septic cardiomyopathy (p < 0.05). These data demonstrate that eRNA plays a crucial role in the pathophysiology of the organ (cardiac) dysfunction in sepsis and RNase and RNH1 may be new therapeutic targets/strategies to reduce the cardiac injury and dysfunction caused by sepsis