Abstract
The newly emergent novel coronavirus disease 2019 (COVID-19) outbreak, which is caused by SARS-CoV-2 virus, has posed a serious threat to global public health and caused worldwide social and economic breakdown. Angiotensin-converting enzyme 2 (ACE2) is expressed in human vascular endothelium, respiratory epithelium, and other cell types, and is thought to be a primary mechanism of SARS-CoV-2 entry and infection. In physiological condition, ACE2 via its carboxypeptidase activity generates angiotensin fragments (Ang 1–9 and Ang 1–7), and plays an essential role in the renin-angiotensin system (RAS), which is a critical regulator of cardiovascular homeostasis. SARS-CoV-2 via its surface spike glycoprotein interacts with ACE2 and invades the host cells. Once inside the host cells, SARS-CoV-2 induces acute respiratory distress syndrome (ARDS), stimulates immune response (i.e., cytokine storm) and vascular damage. SARS-CoV-2 induced endothelial cell injury could exacerbate endothelial dysfunction, which is a hallmark of aging, hypertension, and obesity, leading to further complications. The pathophysiology of endothelial dysfunction and injury offers insights into COVID-19 associated mortality. Here we reviewed the molecular basis of SARS-CoV-2 infection, the roles of ACE2, RAS signaling, and a possible link between the pre-existing endothelial dysfunction and SARS-CoV-2 induced endothelial injury in COVID-19 associated mortality. We also surveyed the roles of cell adhesion molecules (CAMs), including CD209L/L-SIGN and CD209/DC-SIGN in SARS-CoV-2 infection and other related viruses. Understanding the molecular mechanisms of infection, the vascular damage caused by SARS-CoV-2 and pathways involved in the regulation of endothelial dysfunction could lead to new therapeutic strategies against COVID-19.
Highlights
The severe acute respiratory syndrome (SARS) epidemic, which was caused by SARS-CoV, emerged in 2002–2003 in southern China and soon spread to Europe and North America [1,2,3]
G-protein-coupled receptor (GPCR) Mas activation leads to stimulation of major signaling pathways including the activation of phospholipase A (PLA) to generate arachidonic acid (AA), phosphoinositide 3 kinase (PI3K)/AKT
AMP-activated protein kinase (AMPK) was identified as a kinase responsible for GPCR Mas activation leads to stimulation of major signaling pathways including the activation of phospholipase A (PLA) to generate arachidonic acid (AA), phosphoinositide 3 kinase (PI3K)/AKT
Summary
The severe acute respiratory syndrome (SARS) epidemic, which was caused by SARS-CoV, emerged in 2002–2003 in southern China and soon spread to Europe and North America [1,2,3]. Endothelial dysfunction is an important component of a number of human diseases that represents the common denominator of all COVID-19 co-existing conditions such as hypertension, diabetes, and obesity which are major contributing factors for COVID-19-related deaths. Consistent with this hypothesis, other clinical manifestations of COVID-19 include cardiac injury [9] and. Secreted by endothelial cells and that Von Willebrand factor (VWF) levels is significantly elevated in COVID-19 patients SARS-CoV-2 induced vascular damage alone or in combination with pre-existing endothelial dysfunction can lead to multisystem organ failure and death. Key biochemical factors and cellular responses involved in the SARS-CoV-2 induced endothelial damage and endothelial dysfunction are shown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
