Implications of microvascular dysfunction and nitric oxide mediated inflammation in severe COVID-19 infection

Jani, Vinay P.; Muñoz, Carlos; Govender, Krianthan; Williams, Alexander T.; Cabrales, Pedro

doi:10.1016/j.amjms.2022.04.015

Cited by 4 publications

(3 citation statements)

References 49 publications

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“…S3E ). Due to the hypoxic effect and inflammatory responses on ECs [ 28 , 29 ], activation of ECs led to ICAM1 and VCAM1 expression in infected fCBOs (Fig. 3H ).…”

Section: Resultsmentioning

confidence: 99%

Cortical-blood vessel assembloids exhibit Alzheimer’s disease phenotypes by activating glia after SARS-CoV-2 infection

et al. 2023

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A correlation between COVID-19 and Alzheimer’s disease (AD) has been proposed recently. Although the number of case reports on neuroinflammation in COVID-19 patients has increased, studies of SARS-CoV-2 neurotrophic pathology using brain organoids have restricted recapitulation of those phenotypes due to insufficiency of immune cells and absence of vasculature. Cerebral pericytes and endothelial cells, the major components of blood-brain barrier, express viral entry receptors for SARS-CoV-2 and response to systemic inflammation including direct cell death. To overcome the limitations, we developed cortical-blood vessel assembloids by fusing cortical organoid with blood vessel organoid to provide vasculature to brain organoids a nd obtained the characteristics of increased expression of microglia and astrocytes in brain organoids. Furthermore, we observed AD pathologies, including β-amyloid plaques, which were affected by the inflammatory response from SARS-CoV-2 infection. These findings provide an advanced platform to investigate human neurotrophic diseases, including COVID-19, and suggest that neuroinflammation caused by viral infection facilitates AD pathology.

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“…S3E ). Due to the hypoxic effect and inflammatory responses on ECs [ 28 , 29 ], activation of ECs led to ICAM1 and VCAM1 expression in infected fCBOs (Fig. 3H ).…”

Section: Resultsmentioning

confidence: 99%

Cortical-blood vessel assembloids exhibit Alzheimer’s disease phenotypes by activating glia after SARS-CoV-2 infection

et al. 2023

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“… 82 , 83 , 84 An undersulphated glycocalyx may not only increase susceptibility to SARS‐CoV‐2 infection, but would also result in a procoagulant and antifibrinolytic state associated with poorer outcomes. 85 , 86 The competitive action of heparin with heparan sulphate, which is used by SARS‐CoV‐2 to adhere to vascular wall and to bind to ACE2, may explain some of the positive effects of heparin therapy in COVID‐19. Insulin resistance and hyperglycemia affect vascular wall by a series of events.…”

Section: Vascular Dysfunction In Covid‐19 and Diabetesmentioning

confidence: 99%

“…Endothelial glycocalyx is impaired in diabetic condition, and changes in the structure and function of the glycocalyx promote an inflammatory response 82–84 . An undersulphated glycocalyx may not only increase susceptibility to SARS‐CoV‐2 infection, but would also result in a procoagulant and antifibrinolytic state associated with poorer outcomes 85,86 . The competitive action of heparin with heparan sulphate, which is used by SARS‐CoV‐2 to adhere to vascular wall and to bind to ACE2, may explain some of the positive effects of heparin therapy in COVID‐19.…”

Section: Vascular Dysfunction In Covid‐19 and Diabetesmentioning

confidence: 99%

Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID‐19

Bolla

Loretelli

Montefusco

et al. 2022

Diabetes Metabolism Res

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Aims Several reports indicate that diabetes determines an increased mortality risk in patients with coronavirus disease 19 (COVID‐19) and a good glycaemic control appears to be associated with more favourable outcomes. Evidence also supports that COVID‐19 pneumonia only accounts for a part of COVID‐19 related deaths. This disease is indeed characterised by abnormal inflammatory response and vascular dysfunction, leading to the involvement and failure of different systems, including severe acute respiratory distress syndrome, coagulopathy, myocardial damage and renal failure. Inflammation and vascular dysfunction are also well‐known features of hyperglycemia and diabetes, making up the ground for a detrimental synergistic combination that could explain the increased mortality observed in hyperglycaemic patients. Materials and methods In this work, we conduct a narrative review on this intriguing connection. Together with this, we also present the clinical characteristics, outcomes, laboratory and histopathological findings related to this topic of a cohort of nearly 1000 subjects with COVID‐19 admitted to a third‐level Hospital in Milan. Results We found an increased mortality in subjects with COVID‐19 and diabetes, together with an altered inflammatory profile. Conclusions This may support the hypothesis that diabetes and COVID‐19 meet at the crossroads of inflammation and vascular dysfunction. (ClinicalTrials.gov NCT04463849 and NCT04382794).

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Changes in the concentration of sST2, activity of myeloperoxidase, and inducible NO-synthase in serum and lymphocytes as an indicator of disease severity in patients with arterial hypertension and against the background of coronavirus disease

FEDEVYCH,

DENYSENKO,

FOMENKO

et al. 2024

Eksp.Klin.fiziol.biohim

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The prevalence of COVID-19 and its polymorphic clinical manifestations are attributed to a systemic inflammatory response, which also plays a key role in the development of arterial hypertension (AH). The prognosis and effectiveness of treatment in patients with AH and COVID-19 should be assessed based on the levels of inflammatory biomarkers sST2, myeloperoxidase, and iNOS. The aim of the work was to analyze the prognostic value sST2, myeloperoxidase and iNOS levels in the blood serum of patients with arterial hypertension (AH) and COVID-19. Methods. 2 groups of patients were examined: group 1- 36 patients with AH and hypertensive crisis. Group 2 – 35 patients with AH and polysegmental pneumonia on the background of COVID-19. The control group – 16 practically healthy individuals. All patients underwent anthropometry, determination of biochemical blood tests, echocardiography, level of sST2, and activity of iNOS and MPO using ELISA in blood serum and lymphocytes. Results. A 2.4-fold increase in sST2 content in blood serum was noted in AH and 2.9-fold in the background of COVID-19. The level of myeloperoxidase in blood serum increased 2.5 times in hypertension and 3.4 times in coronavirus disease. In lymphocytes, iNOS activity increased 3.25 times in hypertension and 4.3 times in COVID-19. sST2 level has a significant correlation with the size of the left atrium, left ventricle, and ejection fraction in patients with AH. A positive correlation with age was noted in the group of patients with AH and COVID-19. Conclusions. Levels of sST2, iNOS and myeloperoxidase are important markers of the severity of cardiovascular pathology, as well as in COVID-19 patients. In patients with arterial hypertension and in combination with COVID-19, a significant increase in the concentration of sST2, myeloperoxidase and iNOS was observed compared to practically healthy individuals. A significant elevation in myeloperoxidase levels has been noted in patients with AH without coronavirus disease, indicating the utility of its use as a highly sensitive marker for low-intensity inflammation, particularly in arterial hypertension. This makes this marker more promising for use than C-reactive protein.

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Implications of microvascular dysfunction and nitric oxide mediated inflammation in severe COVID-19 infection

Cited by 4 publications

References 49 publications

Cortical-blood vessel assembloids exhibit Alzheimer’s disease phenotypes by activating glia after SARS-CoV-2 infection

Cortical-blood vessel assembloids exhibit Alzheimer’s disease phenotypes by activating glia after SARS-CoV-2 infection

Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID‐19

Changes in the concentration of sST2, activity of myeloperoxidase, and inducible NO-synthase in serum and lymphocytes as an indicator of disease severity in patients with arterial hypertension and against the background of coronavirus disease

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