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

Zechendorf, Elisabeth; Schröder, K.; Stiehler, Lara; Frank, Nadine; Beckers, Christian; Kraemer, Sandra; Dreher, Michael; Kersten, Alexander; Thiemermann, Christoph; Marx, Gernot; Simon, Tim-Philipp; Märtin, Lukas

doi:10.3390/jcm11185261

Cited by 6 publications

(8 citation statements)

References 23 publications

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“…However, it is interesting that heparanase activity is significantly higher in Covid-19 versus non-Covid-19 patients. A recent work reported an average heparanase protein amount serum level of about 100 ng/mL in Covid-19 patients, with no differences between patients with different severities of ARDS 14. In contrast, here we observed that the serum heparanase protein amount is about 200 pg/mL in Covid-19 pneumonia patients.…”

contrasting

confidence: 86%

“…Previous studies have reported an increase in heparanase activity in Covid‐19 patients 13,14 as well as in several other systemic and pulmonary inflammatory conditions 15,16 …”

Section: Resultsmentioning

confidence: 99%

“…In this regard, a recent study by Buijsers et al has demonstrated an association between elevated heparanase activity and plasma heparan sulfate levels that correlated with the need for intensive care unit admission 13 . More recently, Zechendorf et al 14 have demonstrated that heparanase activity and HS levels correlate with Covid‐19 disease severity and outcome.…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies have reported an increase in heparanase activity in Covid-19 patients 13,14 as well as in several other systemic and pulmonary inflammatory conditions. 15,16 In our population, we observed a significant increase (p < 0.01) of HPSE activity and protein amount in SARS-CoV-2 infected subjects with respect to controls (Figure 1A,B).…”

Section: Hpse and Mmps Levels In The Serum Of Covid-19 And Non-covid-...mentioning

confidence: 89%

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Heparanase‐1 and MMPs in Covid‐19 and non‐Covid‐19 pneumonia

Masola,

Marrone,

Condoluci

et al. 2024

Proteoglycan Research

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Together with the ACE2 protein, heparan sulfate present at the level of the glycocalyx in the lung epithelia is considered a cellular “co‐receptor” for the viral spike protein that allows severe acute respiratory syndrome coronavirus 2 (SARS‐CoV) to infect cells. An increase in the amount and activity of heparanase‐1 (HPSE), the only enzyme capable of degrading the heparan sulfate (HS) chains of the glycocalyx and of the extracellular matrix, has been described in the plasma of patients affected by coronavirus disease 2019 (Covid‐19). Furthermore, the activity of matrix metalloproteases, or MMPs, has been related to matrix degradation, oxidative stress, and inflammation in Covid‐19 patients. In this study, we enrolled 26 Covid‐19 patients and 15 controls with diagnosis of non‐SARS‐CoV‐2‐related pneumonia. We evaluated the expression and activity of HPSE and the expression of MMPs in their serum together with other clinical markers of disease and inflammation. Results proved that HPSE expression and activity serum levels were significantly increased, whereas MMP2 and 9 were decreased in Covid‐19 versus non‐Covid‐19 pneumonia patients. In addition, IL‐6 levels were higher, whereas platelet and white blood cells were lower in Covid‐19 with respect to non‐Covid‐19 pneumonia. Moreover, MMP9 but not HPSE (expression and activity) levels were increased in Covid‐19 pneumonia patients with ongoing lung alteration over time. In summary, the present findings indicate that HPSE and MMPs are differentially regulated in Covid‐19 and non‐Covid‐19 pneumonia.

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contrasting

confidence: 86%

“…Previous studies have reported an increase in heparanase activity in Covid‐19 patients 13,14 as well as in several other systemic and pulmonary inflammatory conditions 15,16 …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Section: Hpse and Mmps Levels In The Serum Of Covid-19 And Non-covid-...mentioning

confidence: 89%

See 2 more Smart Citations

Heparanase‐1 and MMPs in Covid‐19 and non‐Covid‐19 pneumonia

Masola,

Marrone,

Condoluci

et al. 2024

Proteoglycan Research

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“…Thirty-five patients with positive SARS-CoV-2 PCR results and intensive care admission were included in this study. This patient population has been described in previous studies by our research group [24][25][26]. The serum samples of patients with COVID-19 infection in the second study population were collected between April 2020 and May 2021.…”

Section: Study Design/populationmentioning

confidence: 99%

A Potential Association between Ribonuclease 1 Dynamics in the Blood and the Outcome in COVID-19 Patients

Zechendorf

Beckers

Frank

et al. 2023

IJMS

Self Cite

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The COVID-19 pandemic caused by the new SARS-CoV-2 coronavirus is the most recent and well-known outbreak of a coronavirus. RNase 1 is a small endogenous antimicrobial polypeptide that possesses antiviral activity against viral diseases. In this study, we investigated a potential association between ribonuclease 1 and the outcome in COVID-19 patients and the impact of increased and decreased RNase 1 levels serum during the course of the disease. Therefore, two patient populations, Cohort A (n = 35) and B (n = 80), were subclassified into two groups, in which the RNase 1 concentration increased or decreased from time point one to time point two. We show that the RNase 1 serum levels significantly increased in the increasing group of both cohorts (p = 0.0171; p < 0.0001). We detect that patients in the increasing group who died had significantly higher RNase 1 serum levels at both time points in Cohort A (p = 0.0170; p = 0.0393) and Cohort B (p = 0.0253; p = 0.0034) than patients who survived. Additionally, we measured a significant correlation of RNase 1 serum levels with serum creatinine as well as creatinine clearance in the increasing and decreasing group at both time points of Cohort A. Based on these results, there is now good evidence that RNase 1 may play a role in renal dysfunction associated with ICU COVID-19 patients and that increasing RNase 1 serum level may be a potential biomarker to predict outcome in COVID-19 patients.

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Lactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis‐Induced Acute Lung Injury

Lu,

Fang,

et al. 2024

Advanced Science

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Circulating lactate is a critical biomarker for sepsis‐induced acute lung injury (S‐ALI) and is strongly associated with poor prognosis. However, whether elevated lactate directly promotes S‐ALI and the specific mechanism involved remain unclear. Here, this work shows that lactate causes pulmonary endothelial glycocalyx degradation and worsens ALI during sepsis. Mechanistically, lactate increases the lactylation of K18 of histone H3, which is enriched at the promoter of EGR1 and promotes its transcription, leading to upregulation of heparanase in pulmonary microvascular endothelial cells. In addition, multiple lactylation sites are identified in EGR1, and lactylation is confirmed to occur mainly at K364. K364 lactylation of EGR1 facilitates its interaction with importin‐α, in turn promoting its nuclear localization. Importantly, this work identifies KAT2B as a novel lactyltransferase whose GNAT domain directly mediates the lactylation of EGR1 during S‐ALI. In vivo, suppression of lactate production or genetic knockout of EGR1 mitigated glycocalyx degradation and ALI and improved survival outcomes in mice with polymicrobial sepsis. Therefore, this study reveals that the crosstalk between metabolic reprogramming in endothelial cells and epigenetic modifications plays a critical role in the pathological processes of S‐ALI.

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

Cited by 6 publications

References 23 publications

Heparanase‐1 and MMPs in Covid‐19 and non‐Covid‐19 pneumonia

Heparanase‐1 and MMPs in Covid‐19 and non‐Covid‐19 pneumonia

A Potential Association between Ribonuclease 1 Dynamics in the Blood and the Outcome in COVID-19 Patients

Lactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis‐Induced Acute Lung Injury

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