The Contribution of Endothelial Dysfunction in Systemic Injury Subsequent to SARS-Cov-2 Infection

Abstract

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells, which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of a SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to a detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with the ACE2 receptor located in the endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function, which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease, leading to irreversible tissue damage and death of people with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated with the interaction of SARS CoV-2 with the ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

From Metabolic Syndrome to Neurological Diseases: Role of Autophagy

“…Vascular endothelium cells (VEC) play a fundamental role in the human body; ensuring the regulation of vasomotor functions, the maintenance of vessel walls, anti-platelet aggregation, and endocrine functions. Numerous harmful stimuli can lead to endothelial cell dysfunction (ECD) with consequential increases in the risk of many diseases including cardiovascular diseases ( Vykoukal and Davies, 2011 ; Khaddaj Mallat et al, 2017 ; Kaplan et al, 2018 ; Maiuolo et al, 2020a ). In MetS patients, the ECD is a specific early pathophysiological indicator of cardiovascular disorders; its recognition and early intervention are of extreme importance in the prevention, treatment, and prognosis of cardiovascular diseases ( Wei et al, 2014 ; Dalal et al, 2020 ).…”

Evaluation of oxidative stress markers in hospitalized patients with moderate and severe COVID-19

“…According to WHO, patients have been categorized in the range from asymptomatic or mild to moderate, severe or critical [1]. In general, SARS-CoV-2 virus attacks almost every system in the human body [9][10][11]. The outcome of the disease in many patients is correlated with laboratory and clinical properties of a cytokine storm that triggers pro-inflammatory condition leading to excessive production of reactive oxygen species (ROS) that is linked with severe tissue damage.…”

COVID-19–Associated Endothelial Dysfunction and Microvascular Injury

“…Coagulation abnormalities and disruption of factors released by endothelial cells represent also the common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events, including acute cardiac injury, stroke, heart failure, arrhythmias, and cardiomyopathies. In particular, the molecular interaction of SARS-CoV-2 with the ACE2 receptor located in the endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function, which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels ( 34 ).…”