scholarly journals Endothelin-1 is Increased in the Plasma of Patients Hospitalized with Covid-19

Author(s):  
George Abraham ◽  
Rhoda Kuc ◽  
Magnus Althage ◽  
Peter Greasley ◽  
Philip Ambery ◽  
...  

Importance The coronavirus disease 2019 (Covid-19) pandemic continues to place a devastating strain on healthcare services worldwide and there remains an ongoing requirement for new treatments. A key mechanism recognised in progressive severe disease is virus-induced endothelial dysregulation. Endothelin-1 (ET-1), being the most highly expressed peptide in endothelial cells and potent vasoconstrictor of human blood vessels, represents a potential therapeutic target through the use of Endothelin receptor antagonists. Objective To investigate the association of plasma ET-1 with Covid-19 disease severity Design Retrospective longitudinal cohort study of Covid-19 patients divided into Group A (asymptomatic or symptoms not requiring hospitalisation), Group B (symptoms requiring hospitalisation) and Group C (symptoms requiring supplemental oxygen therapy or assisted ventilation) recruited between March and July 2020 (the first wave of the Covid-19 pandemic in the UK). Data were compared with a contemporaneous cross-section of non-infected volunteers (Controls). Setting Single Tertiary National Health Service Hospital. Participants Tissue banked plasma samples were obtained from 194 patients. Exposures Quantitation of ET-1 in plasma by specific enzyme linked immunosorbent assay. Main outcome and measures Pairwise comparison of ET-1 levels (median [IQR]) between patient categories, and subgroups defined by clinical outcomes. Results Baseline ET-1 plasma levels (pg/ml) were elevated in patients requiring hospitalisation compared with controls and patients with asymptomatic or mild infection (Group B: 1.59 [1.13-1.98], and Group C: 1.65 [1.02-2.32] versus controls: 0.68 [0.47-0.87], p=<0.001 and Group A: 0.72 [0.57-1.10], p=<0.001). ET-1 levels were also elevated in patients that died (2.09 [1.66-3.15]), developed acute kidney (1.70 [1.07-2.36]) or myocardial injury (1.50 [0.92-2.28]) compared with patients with an uncomplicated infection (1.00 [0.61-1.57], p=<0.01). Amongst surviving hospitalised patients, ET-1 concentrations decreased when measured at 28 days (Group B: 0.86 [0.60-1.61] and Group C: 1.17 [0.66-1.62] versus baseline, p=<0.05) and 90 days (Group B: 0.69 [0.59-1.38] and Group C: 1.01 [0.64-1.21] versus baseline, p=<0.05). Conclusions and relevance Hospitalised Covid-19 patients demonstrate elevated ET-1 levels during the acute phase of infection and this is associated with increasing clinical severity of the disease. The results support the hypothesis that endothelin receptor antagonists may be beneficial for certain Covid-19 patients.

2020 ◽  
Vol 98 (9) ◽  
pp. 570-578
Author(s):  
Michael R. Dashwood ◽  
Andrzej Loesch

The saphenous vein is the most commonly used bypass graft in patients with coronary artery disease. During routine coronary artery bypass, grafting the vascular damage inflicted on the vein is likely to stimulate the release of endothelin-1, a potent endothelium-derived vasoconstrictor that also possesses cell proliferation and inflammatory properties, conditions associated with vein graft failure. In both in vitro and in vivo studies, endothelin receptor antagonists reduce neointimal thickening. The mechanisms underlying these observations are multifactorial and include an effect on cell proliferation and cell/tissue damage. Much of the data supporting the beneficial action of endothelin-1 receptor antagonism at reducing intimal thickening and occlusion in experimental vein grafts were published over 20 years ago. The theme of the recent ET-16 conference in Kobe was “Visiting Old and Learning New”. This short review article provides an overview of studies showing the potential of endothelin receptor antagonists to offer an adjuvant therapeutic approach for reducing saphenous vein graft failure and poses the question why this important area of research has not been translated from bench to bedside given the potential benefit for coronary artery bypass patients.


2014 ◽  
Vol 63 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Agata Kowalczyk ◽  
Paulina Kleniewska ◽  
Michal Kolodziejczyk ◽  
Beata Skibska ◽  
Anna Goraca

2000 ◽  
Vol 36 (Supplement 1) ◽  
pp. S292-S296 ◽  
Author(s):  
Terry J. Opgenorth ◽  
Jerry L. Wessale ◽  
Douglas B. Dixon ◽  
Andrew L. Adler ◽  
Samuel V. Calzadilla ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document