Role of Endothelial Cells in Acute and Chronic Thrombosis

Abstract

Haemostasis encompasses a set of strictly regulated actions, such as vasoconstriction, platelet activation and blood coagulation. Endothelial cells play a crucial role in all of these processes and are an integral part of the vascular response to injury resulting in thrombus formation. Healthy endothelium expresses mediators to prevent platelet activation, including prostacyclin and nitric oxide, and to inhibit coagulation, such as thrombomodulin or RNase1. Upon activation, endothelial cells expose von Willebrand factor, integrins and other receptors to interact with activated platelets, erythrocytes and coagulation factors, respectively, resulting in blood clot formation. The endothelial cell response to cytokines and growth factors released from activated platelets and immune cells abundantly present in arterial and venous thrombi also plays an important role for thrombus resolution, whereas failure to completely resolve thrombi may initiate fibrotic remodelling and chronic vascular occlusion both in the arterial and venous tree. Therefore, endothelial cells are increasingly recognized as potential target to prevent thrombotic events and to accelerate thrombus resolution. Here, we discuss recent publications from our group in the context of other studies on the role of the endothelium during acute and chronic thrombotic events.

The Endothelium as a Driver of Liver Fibrosis and Regeneration

“…Healthy endothelial cells express molecules that prevent platelet activation, coagulation and thrombus formation [126][127][128][129][130]. During endothelial dysfunction, LSEC lose their antithrombotic phenotype altering the expression of pro-and anti-thrombotic factors [2,130,131].…”

“…Healthy endothelial cells express molecules that prevent platelet activation, coagulation and thrombus formation [126][127][128][129][130]. During endothelial dysfunction, LSEC lose their antithrombotic phenotype altering the expression of pro-and anti-thrombotic factors [2,130,131]. Dysfunctional LSEC expose von Willebrand factor, integrins and other receptors that interact with activated platelets, ultimately leading to blood clot formation [132,133] as well as attenuating the expression of thrombomodulin, NO or PGI2 [132].…”

Endothelial Ribonuclease 1 in Cardiovascular and Systemic Inflammation

“…These atherosclerotic lesions can further disrupt to provoke thrombus formation (Libby et al, 2019). Healthy ECs contribute to the regulation of coagulation and thrombus formation to maintain vascular homeostasis by secretion of both pro-and antithrombotic factors (Bochenek and Schafer, 2019). However, prolonged vessel injury and inflammation result in EC dysfunction, causing a pathological outcome of this process by complete vessel occlusion and development of consequential pathologies like myocardial infarction (MI) or stroke (Bochenek and Schafer, 2019;Libby et al, 2019).…”

“…Healthy ECs contribute to the regulation of coagulation and thrombus formation to maintain vascular homeostasis by secretion of both pro-and antithrombotic factors (Bochenek and Schafer, 2019). However, prolonged vessel injury and inflammation result in EC dysfunction, causing a pathological outcome of this process by complete vessel occlusion and development of consequential pathologies like myocardial infarction (MI) or stroke (Bochenek and Schafer, 2019;Libby et al, 2019). In this context, eRNA was identified to be enriched at sites of vascular injury, acting as a prothrombotic and proinflammatory factor (Zernecke and Preissner, 2016).…”

COVID-19 — Endothelial Axis and Coronary Artery Bypass Graft Patency: a Target for Therapeutic Intervention?

“…In CABG patients, SARS-CoV-2 could bind ACE2 in SV and, therefore, influence the incidence of graft failure through an increase in vascular inflammation and vascular and endothelial dysfunction. Moreover, the inflammatory effects of cytokines also result in activated vascular endothelial cells and endothelial injury with resultant prothrombotic properties [ 37 ] . Also, the increased release of pro-inflammatory cytokines, including TNFα and IL-6, from human SV under inflammatory conditions has been shown, suggesting the possible interaction of vascular inflammation, endothelial dysfunction, and the risk of thrombosis in SV graft failure [ 38 ] .…”