Endothelial Dysfunction in COVID-19: Potential Mechanisms and Possible Therapeutic Options

Life, Journal Year: 2022, Volume and Issue: 12(10), P. 1605 - 1605

Published: Oct. 14, 2022

SARS-CoV-2, a novel coronavirus found in Wuhan (China) at the end of 2019, is etiological agent current pandemic that heterogeneous disease, named disease 2019 (COVID-19). SARS-CoV-2 affects primarily lungs, but it can induce multi-organ involvement such as acute myocardial injury, myocarditis, thromboembolic eventsandrenal failure. Hypertension, chronic kidney diabetes mellitus and obesity increase risk severe complications COVID-19. There no certain explanation for this systemic COVID-19 involvement, could be related to endothelial dysfunction, due direct (endothelial cells are infected by virus) indirect damage (systemic inflammation) factors. Angiotensin-converting enzyme 2 (ACE2), expressed human endothelium, has fundamental role respiratory syndrome (SARS-CoV-2) infection. In fact, ACE2 used receptor leading downregulation these receptors on cells; once inside, virus reduces integrity tissue, with exposure prothrombotic molecules, platelet adhesion, activation coagulation cascades and, consequently, vascular damage. Systemic microangiopathy thromboembolism lead failure an elevated death. Considering crucial immunological response developing form COVID-19, review, we will attempt clarify underlying pathophysiological mechanisms.

Language: Английский

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Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(3)

Published: Feb. 20, 2022

Abstract Numerous pharmaceutical drugs have been repurposed for use as treatments COVID-19 disease. These not consistently demonstrated high efficacy in preventing or treating this serious condition and all side effects to differing degrees. We encourage the continued consideration of antioxidant anti-inflammatory agent, melatonin, a countermeasure SARS-CoV-2 infection. More than 140 scientific publications identified melatonin likely useful agent treat Moreover, cited provide rationale prophylactic against condition. Melatonin has pan-antiviral it diminishes severity viral infections reduces death animals infected with numerous different viruses, including three coronaviruses. Network analyses, which compared used humans, also predicted that would be most effective preventing/treating COVID-19. Finally, when seriously patients were treated either alone combination other medications, these reduced infection, lowered rate, shortened duration hospitalization. Melatonin’s ability arrest may reduce health care exhaustion by limiting need Importantly, safety profile over wide range doses lacks significant toxicity. Some molecular processes resists infection are summarized. The authors believe available, potentially beneficial drugs, lack toxicity should pandemics such caused SARS-CoV-2.

Language: Английский

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Persistent Lung Injury and Prothrombotic State in Long COVID

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

Lung injury may persist during the recovery period of COVID-19 as shown through imaging, six-minute walk, and lung function tests. The pathophysiological mechanisms leading to long COVID have not been adequately explained. Our aim is investigate basis pulmonary susceptibility sequelae possibility that prothrombotic states influence long-term symptoms COVID-19. patient’s lungs remain vulnerable stage due persistent shedding virus, inflammatory environment, state, subsequent repair blood-air barrier. transformation inflammation proliferation fibrosis, hypoxia-involved vascular remodeling, endothelial cell damage, phosphatidylserine-involved hypercoagulability, continuous changes in serological markers all contribute post-discharge injury. Considering important role microthrombus arteriovenous thrombus process functional lesions organic lesions, we further study states, including activation affect COVID. Early use combined anticoagulant antiplatelet therapy a promising approach reduce incidence sequelae. Essentially, early treatment can block occurrence thrombotic events. Because impeded circulation causes large pressure imbalances over alveolar membrane infiltration plasma into cavity, inhibition events prevent hypertension, formation hyaline membranes, consolidation.

Language: Английский

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Links between Vitamin K, Ferroptosis and SARS-CoV-2 Infection

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 733 - 733

Published: March 16, 2023

Ferroptosis is a recently discovered form of programmed cell death. It characterized by the accumulation iron and lipid hydroperoxides in cells. Vitamin K known to have antioxidant properties plays role reducing oxidative stress, particularly membranes. reduces level reactive oxygen species modulating expression enzymes. Additionally, vitamin decreases inflammation potentially prevents ferroptosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading disease 2019 (COVID-19) associated with oxidant–antioxidant imbalance. Studies shown that intensified ferroptosis occurs various tissues cells affected COVID-19. supplementation during SARS-CoV-2 may positive effect on severity disease. Preliminary research suggests reduce peroxidation inhibit ferroptosis, contributing its therapeutic effects COVID-19 patients. The links between K, require further investigation, context developing potential treatment strategies for

Language: Английский

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N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions

Journal of Infection and Public Health, Journal Year: 2022, Volume and Issue: 15(12), P. 1477 - 1483

Published: Nov. 12, 2022

Language: Английский

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Relationship Between Endothelial and Angiogenesis Biomarkers Envisage Mortality in a Prospective Cohort of COVID-19 Patients Requiring Respiratory Support

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: March 16, 2022

Endothelial damage and angiogenesis are fundamental elements of neovascularisation fibrosis observed in patients with coronavirus disease 2019 (COVID-19). Here, we aimed to evaluate whether early endothelial angiogenic biomarkers detection predicts mortality major cardiovascular events COVID-19 requiring respiratory support. Changes serum syndecan-1, thrombomodulin, factor concentrations were analysed during the first 24 h 10 days after hospitalisation high-flow nasal oxygen or mechanical ventilation. Also, performed an exploratory evaluation migration process induced by patients' using cell culture model. In 43 patients, mean syndecan-1 concentration was 40.96 ± 106.9 ng/mL a 33.9% increase (49.96 58.1 ng/mL) at day 10. Both increases significant compared healthy controls (Kruskal-Wallis p < 0.0001). We Angiopoietin-2, human vascular growth (VEGF), hepatocyte (HGF) h, decrease tissue inhibitor metalloproteinases-2 (TIMP-2) that remained days. An Interleukin-8 (IL-8) on 10th accompanied high HGF also noted. The incidence myocardial injury pulmonary thromboembolism 55.8 20%, respectively. in-hospital deaths 16.3%. Biomarkers showed differences severity COVID-19. Syndecan-1, platelet-derived (PDGF), VEGF, Ang-2 predicted mortality. A multiple logistic regression model TIMP-2 PDGF had positive negative predictive powers 80.9 70%, respectively, for None thromboembolism. proteome profiler array found changes large number chemoattractants. Finally, samples from increased individuals. Chemoattractants cells. Trials needed confirmation, as this poses therapeutic target SARS-CoV-2.

Language: Английский

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COVID-19: Not a thrombotic disease but a thromboinflammatory disease

Upsala Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 129

Published: Jan. 22, 2024

While Coronavirus Disease in 2019 (COVID-19) may no longer be classified as a global public health emergency, it still poses significant risk at least due to its association with thrombotic events. This study aims reaffirm our previous hypothesis that COVID-19 is fundamentally disease. To accomplish this, we have undertaken an extensive literature review focused on assessing the comprehensive impact of entire hemostatic system. Our analysis revealed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection significantly enhances initiation thrombin generation. However, noteworthy generation modulated by specific anticoagulants present patients’ plasma. Consequently, higher levels fibrinogen appear play more pivotal role promoting coagulation COVID-19, opposed Furthermore, viral can stimulate platelet activation either through widespread dissemination from lungs other organs or localized effects platelets themselves. An imbalance between Von Willebrand Factor (VWF) and ADAMTS-13 also contributes exaggerated response this disease, addition elevated D-dimer levels, coupled increase fibrin viscoelasticity. paradoxical phenotype has been identified ‘fibrinolysis shutdown’. clarify pathogenesis underlying these disorders examined published data, tracing reaction process relevant proteins cells, ACE2-dependent invasion, induced tissue inflammation, endothelial injury, innate immune responses, occurrence We therefrom understand should viewed disease solely based abnormalities clot formation proteolysis. Instead, regarded thromboinflammatory disorder, incorporating both classical elements cellular inflammation their intricate interactions coagulopathy.

Language: Английский

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COVID-19 and Pulmonary Angiogenesis: The Possible Role of Hypoxia and Hyperinflammation in the Overexpression of Proteins Involved in Alveolar Vascular Dysfunction

Viruses, Journal Year: 2023, Volume and Issue: 15(3), P. 706 - 706

Published: March 8, 2023

COVID-19 has been considered a vascular disease, and inflammation, intravascular coagulation, consequent thrombosis may be associated with endothelial dysfunction. These changes, in addition to hypoxia, responsible for pathological angiogenesis. This research investigated the impact of on function by analyzing post-mortem lung samples from 24 patients, 10 H1N1pdm09 11 controls. We evaluated, through immunohistochemistry technique, tissue immunoexpressions biomarkers involved dysfunction, microthrombosis, angiogenesis (ICAM-1, ANGPT-2, IL-6, IL-1β, vWF, PAI-1, CTNNB-1, GJA-1, VEGF, VEGFR-1, NF-kB, TNF-α HIF-1α), along histopathological presence activation, layer hypertrophy. Clinical data patients were also observed. The results showed that was increased immunoexpression compared H1N1 CONTROL groups. Microthrombosis hypertrophy found more prevalent patients. study concluded immunothrombosis might play key role progression outcome, particularly who die disease.

Language: Английский

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Roles of Interleukin-6-mediated immunometabolic reprogramming in COVID-19 and other viral infection-associated diseases

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 110, P. 109005 - 109005

Published: June 28, 2022

Language: Английский

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Coronavirus Disease 2019-Associated Coagulopathy

Microorganisms, Journal Year: 2022, Volume and Issue: 10(8), P. 1556 - 1556

Published: Aug. 2, 2022

Coronavirus disease 2019 (COVID-19)-associated coagulopathy is an acute illness characterized by thrombosis with or without hemorrhage after COVID-19 infection. Clinical symptoms of COVID-19-associated can occur at any anatomical site. Various forms venous thromboembolism, including deep vein and pulmonary embolism, are common in acutely ill patients COVID-19. Laboratory findings, such as D-dimer platelet counts, help diagnose coagulopathy. Anticoagulation using direct oral anticoagulants low-molecular-weight heparin essential for the treatment Prophylactic important preventing severe In particular, early initiation prophylactic anticoagulation improve survival rates risk serious bleeding events.

Language: Английский

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