NOX2 and NOX5 are increased in cardiac microvascular endothelium of deceased COVID-19 patients

Jiang, Zhu; Wu, Linghe; Leeden, Britt van der; Rossum, Albert C. van; Niessen, H.W.M.; Krijnen, Paul A J

doi:10.1016/j.ijcard.2022.10.172

Cited by 7 publications

(11 citation statements)

References 44 publications

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“…The lungs are thought to be the main target, but ACE2 receptor expression in the kidneys, heart, and bladder explains multi-organ involvement from infection [1]. Studies have also found expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase isozymes 2, 4, and 5 (NOX2, NOX4, and NOX5) in human cardiac microvascular endothelium [9]. These enzymes play a role in producing reactive oxygen species (ROS), and over-activation may contribute to microvascular endothelial dysfunction [9].…”

Section: Discussionmentioning

confidence: 99%

The Discovery of an Intracardiac Thrombus Following a Mild COVID-19 Infection: A Case Report and Review of Literature

Bhandari¹,

Abbas²,

Alfarone³

et al. 2023

Cureus

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19) is a viral disease that predominantly affects the respiratory system, but extrapulmonary manifestations have been increasingly reported over the course of the pandemic. Common extrapulmonary manifestations include the gastrointestinal, cardiovascular, and neurological systems, such as diarrhea, rashes, loss of smell/taste, myalgia, acute kidney injury, cardiac arrhythmias, or heart failure. COVID-19 infection is associated with an increased risk of thromboembolic events, especially in the setting of severe disease. We present a case of a 42-year-old female who recently tested positive for COVID-19 infection and presented to the clinic with complaints of palpitations that started after her diagnosis. An electrocardiogram done in the clinic showed sinus rhythm, and the patient was placed on an event monitor, which showed no evidence of tachyarrhythmia. A transthoracic echocardiogram (TTE) done as part of the workup showed a large thrombus in the right ventricular outflow tract attached to the ventricular side of the pulmonic valve. The patient was started on a therapeutic dose of apixaban at 10 mg twice a day (BID) for seven days and 5 mg twice a day afterward.

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Section: Discussionmentioning

confidence: 99%

The Discovery of an Intracardiac Thrombus Following a Mild COVID-19 Infection: A Case Report and Review of Literature

Bhandari¹,

Abbas²,

Alfarone³

et al. 2023

Cureus

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“…Specifically, compared to controls, SARS-CoV-2 infected patients displayed overactivation of NOX2, which was more marked in subjects with thrombotic complications, indicating a role in thrombotic-related ischemic events . More recently, the induction of NOX2 and NOX5 in the cardiac microvascular endothelium was also reported, even if the exact roles of NOXs in the pathogenesis of COVID-19 remain to be elucidated …”

Section: Noxs and Diseasesmentioning

confidence: 97%

“…103 More recently, the induction of NOX2 and NOX5 in the cardiac microvascular endothelium was also reported, even if the exact roles of NOXs in the pathogenesis of COVID-19 remain to be elucidated. 104 NOX and Neurodegeneration. To maintain homeostasis and neuronal cell function, the human nervous system consumes about 20% of the amount of oxygen used by the body, causing a large production of ROS.…”

Section: ■ Architecture Of the Catalytic Corementioning

confidence: 99%

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NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors

Cipriano,

Viviano,

Feoli

et al. 2023

J. Med. Chem.

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NADPH oxidases (NOXs) form a family of electrontransporting membrane enzymes whose main function is reactive oxygen species (ROS) generation. Strong evidence suggests that ROS produced by NOX enzymes are major contributors to oxidative damage under pathologic conditions. Therefore, blocking the undesirable actions of these enzymes is a therapeutic strategy for treating various pathological disorders, such as cardiovascular diseases, inflammation, and cancer. To date, identification of selective NOX inhibitors is quite challenging, precluding a pharmacologic demonstration of NOX as therapeutic targets in vivo. The aim of this Perspective is to furnish an updated outlook about the small-molecule NOX inhibitors described over the last two decades. Structures, activities, and in vitro/in vivo specificity are discussed, as well as the main biological assays used. ■ SIGNIFICANCE• ROS produced by NOXs are major contributors to oxidative damage in pathologic conditions. • Therefore, blocking the undesirable actions of these enzymes is a therapeutic strategy for treating various pathological disorders. • The aim of this Perspective is to provide insight on NOX proteins as targets and an overview and update on the current status of NOX inhibitors, including challenges and potential strategic directions for future progress in the field.

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“…17β-estradiol completely reversed S protein-induced activation of NOX2 and reactive oxygen species production, angiotensin-converting enzyme 2 (ACE2) upregulation and induction of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1) in endothelial cells, thus attenuating endothelial dysfunction [ 120 ]. More recently, NOX2 and NOX5 have been shown to be increased in the cardiac microvascular endothelium of deceased COVID-19 patients, which may contribute to their previously reported cardio-microvascular dysfunction [ 121 ]. Recently, it has been shown that patients with COVID-19 have significant higher markers of oxidative stress (such as soluble Nox2-derived peptide and hydrogen peroxide) and inflammation (TNF-α and IL-6), while, conversely, flow-mediated dilation, hydrogen peroxide breakdown activity and nitric oxide (NO) bioavailability were shown to be significantly lower [ 122 ].…”

Section: Covid-19 Obesity Inflammation and Oxidative Stress In Cardio...mentioning

confidence: 99%

Cross-Talk of NADPH Oxidases and Inflammation in Obesity

Morawietz¹,

Brendel²,

Diaba-Nuhoho

et al. 2023

Antioxidants

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Obesity is a major risk factor for cardiovascular and metabolic diseases. Multiple experimental and clinical studies have shown increased oxidative stress and inflammation linked to obesity. NADPH oxidases are major sources of reactive oxygen species in the cardiovascular system and in metabolically active cells and organs. An impaired balance due to the increased formation of reactive oxygen species and a reduced antioxidative capacity contributes to the pathophysiology of cardiovascular and metabolic diseases and is linked to inflammation as a major pathomechanism in cardiometabolic diseases. Non-alcoholic fatty liver disease is particularly characterized by increased oxidative stress and inflammation. In recent years, COVID-19 infections have also increased oxidative stress and inflammation in infected cells and tissues. Increasing evidence supports the idea of an increased risk for severe clinical complications of cardiometabolic diseases after COVID-19. In this review, we discuss the role of oxidative stress and inflammation in experimental models and clinical studies of obesity, cardiovascular diseases, COVID-19 infections and potential therapeutic strategies.

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NOX2 and NOX5 are increased in cardiac microvascular endothelium of deceased COVID-19 patients

Cited by 7 publications

References 44 publications

The Discovery of an Intracardiac Thrombus Following a Mild COVID-19 Infection: A Case Report and Review of Literature

The Discovery of an Intracardiac Thrombus Following a Mild COVID-19 Infection: A Case Report and Review of Literature

NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors

Cross-Talk of NADPH Oxidases and Inflammation in Obesity

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