https://orcid.org/0000-0001-9080-1466
Figures & data
Figure 1. Pathophysiologic mechanisms of COVID-19 and proposed mechanisms of defibrotide in treatment of COVID-19. SARS-CoV-2 directly infects endothelial cells by binding to ACE2, leading to endocytosis and degradation of ACE2, and loss of ACE2 permits dysregulation of the Angiotensin II signaling axis [Citation34]. Angiotensin-II levels are increased in patients with SARS-CoV-2, likely secondary to decreased conversion to Angiotensin 1–7; increased Angiotensin-II levels lead to activation of p38/MAPK, which contributes to endotheliitis, vasoconstriction, production of inflammatory cytokines, expression of adhesion molecules VCAM-1 and ICAM-1, release of Weibel Palade bodies, and up-regulation of Heparanase-1 [Citation36]. Defibrotide inhibits activity of p38/MAPK, reduces production of proinflammatory cytokines, decreases expression of adhesion molecules, diminishes Weibel Palade body release, and limits expression and activity of Heparanase-1 [Citation2,Citation7–12]. (Created with BioRender.com)
![Figure 1. Pathophysiologic mechanisms of COVID-19 and proposed mechanisms of defibrotide in treatment of COVID-19. SARS-CoV-2 directly infects endothelial cells by binding to ACE2, leading to endocytosis and degradation of ACE2, and loss of ACE2 permits dysregulation of the Angiotensin II signaling axis [Citation34]. Angiotensin-II levels are increased in patients with SARS-CoV-2, likely secondary to decreased conversion to Angiotensin 1–7; increased Angiotensin-II levels lead to activation of p38/MAPK, which contributes to endotheliitis, vasoconstriction, production of inflammatory cytokines, expression of adhesion molecules VCAM-1 and ICAM-1, release of Weibel Palade bodies, and up-regulation of Heparanase-1 [Citation36]. Defibrotide inhibits activity of p38/MAPK, reduces production of proinflammatory cytokines, decreases expression of adhesion molecules, diminishes Weibel Palade body release, and limits expression and activity of Heparanase-1 [Citation2,Citation7–12]. (Created with BioRender.com)](/cms/asset/4a1aebac-bad9-4b33-88c9-973cde9fc7fc/iett_a_1944101_f0001_oc.jpg)