Graphical abstract
Some of the mechanisms and conditions underlying endothelial dysfunction.
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A
- Human skin capillaries, visualized with high-resolution intravital color microscopy in the finger of a patient with obesity, metabolic syndrome, and coronary artery disease.
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B
- In a healthy control: the reduced number of capillaries can be noticed in A compared to B.
Dear Editor,
Amidst the pandemic that has mesmerized the entire world, as it has not spared anyone according to any specific characteristic, some conditions have in fact emerged as risk factors for a complicated evolution of COVID-19. Cardiovascular and metabolic diseases, including hypertension and diabetes, have been associated with more severe presentations and/or adverse prognosis [1].
As Li et al. point out in their recent paper [2], there is a complex network of predisposing factors in patients with cardiovascular disease. However, an important player in the scenario of cardiovascular and metabolic diseases was overlooked. Endothelial dysfunction – the impairment of the ability of the endothelium to maintain vascular homeostasis – is the final common pathway for diabetes/insulin resistance, hypertension, and dyslipidemia. The inflammatory state, increased oxidative stress, altered nitric oxide bioavailability, and insulin resistance are key factors of endothelial dysfunction [3,4]. Additionally, as SARS-CoV-2 infects host cells by means of the transmembrane angiotensin-converting enzyme (ACE)-II receptor, which is expressed in endothelial cells, there is substrate for a direct pathogenic effect of the virus [5]. Other noxious influences over the endothelium include effects of proinflammatory cytokines (“cytokine storm”), resulting in vascular endothelial cell apoptosis and leading to lung microvascular dysfunction, vascular leakage, alveolar edema, and ultimately hypoxia. Moreover, proinflammatory cytokines increase the expression of adhesion molecules, resulting in endothelial activation, procoagulant and proadhesive changes, worsening microvascular flow and, consequently, tissue perfusion. Pulmonary endothelial activation has been recently demonstrated in an autopsy study of 10 patients with COVID-19. Histological findings revealed exudative/proliferative diffuse alveolar damage, but endothelial tumefaction in pulmonary capillaries and fibrinous thrombi in small pulmonary arterioles were also found [6].
The chronic impairment of systemic endothelial function in patients with cardiovascular and metabolic disorders, when aggravated by the acute, noxious effects of SARS-CoV-2 over the endothelium, may explain their worse outcomes in COVID-19. Therefore, the recognition of the role of endothelial dysfunction in the pathophysiology of COVID-19 in patients with cardiometabolic disorders is relevant, and may offer a new target for therapies aiming at minimizing the severity of the infection in this patient population.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Handling Editor: A. Siani
References
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