Protective Role of Nitric Oxide Against Cardiac Arrhythmia - An Update

Burger, Dylan

doi:10.2174/1875042701103010038

Cited by 4 publications

(4 citation statements)

References 128 publications

(156 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First NO-related effects on hypoxia- and reoxygenation-induced arrhythmias, especially ventricular arrhythmias, were reported in the 1970s when nitroglycerin was shown to be effective in these conditions (for review see [15]). Later several groups used NO precursor L-arginine as well as L-arginine methyl ester to cope with experimental ventricular arrhythmia [16, 17].…”

Section: Resultsmentioning

confidence: 99%

Protective Effects of Dinitrosyl Iron Complexes under Oxidative Stress in the Heart

Kapelko

Лакомкин

Абрамов

et al. 2017

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Background. Nitric oxide can successfully compete with oxygen for sites of electron-transport chain in conditions of myocardial hypoxia. These features may prevent excessive oxidative stress occurring in cardiomyocytes during sudden hypoxia-reoxygenation. Aim. To study the action of the potent stable NO donor dinitrosyl iron complex with glutathione (Oxacom®) on the recovery of myocardial contractile function and Ca2+ transients in cardiomyocytes during hypoxia-reoxygenation. Results. The isolated rat hearts were subjected to 30 min hypoxia followed by 30 min reoxygenation. The presence of 30 nM Oxacom in hypoxic perfusate reduced myocardial contracture and improved recovery of left ventricular developed pressure partly due to elimination of cardiac arrhythmias. The same Oxacom concentration limited reactive oxygen species generation in hypoxic cardiomyocytes and increased the viability of isolated cardiomyocytes during hypoxia from 12 to 52% and after reoxygenation from 0 to 40%. Oxacom prevented hypoxia-induced elevation of diastolic Ca2+ level and eliminated Ca2+ transport alterations manifested by slow Ca2+ removal from the sarcoplasm and delay in cardiomyocyte relaxation. Conclusion. The potent stable NO donor preserved cardiomyocyte integrity and improved functional recovery at hypoxia-reoxygenation both in the isolated heart and in cardiomyocytes mainly due to preservation of Ca2+ transport. Oxacom demonstrates potential for cardioprotection during hypoxia-reoxygenation.

show abstract

Section: Resultsmentioning

confidence: 99%

Protective Effects of Dinitrosyl Iron Complexes under Oxidative Stress in the Heart

Kapelko

Лакомкин

Абрамов

et al. 2017

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Additional consequences of the overproduction of ORF8 in Ds patients with COVID-19 are as follows: 1) the several structural similarities of this viral protein with the nitric oxide synthase can alter the serum concentrations of NO, reducing the protective function of this gas against arrhythmias ( Burger and Feng, 2011 ); 2) ORF8 can also be an important factor to aggravate the cytokine storm due its high degree of structural mimicry with immunoglobulins and their receptors ( Valcarcel et al, 2021 ), with the subsequent small protoembolic events that cause a cardiovascular damage similar to that of older Ds patients never infected with Covid-19 ( Colvin and Yeager, 2017 ; De Toma and Dierssen, 2020 ). 3) Taking into consideration that chromosome 21 also harbors multiple genes involved in the immune response, and their overexpression induces the dysregulation of interleukins IL-10, IL-22, and IL-26 prior to infection ( De Weerd and Nguyen, 2020 ), the presence of high levels of ORF8 could also be an important factor to aggravate the cytokine storm in Ds patients with COVID-19.…”

mentioning

confidence: 99%

ORF8 and Health Complications of COVID-19 in Down Syndrome Patients

et al. 2022

View full text Add to dashboard Cite

In that work, ORF8 was characterized as a notable SARS-CoV-2 protein able to downregulate the function of MHC-I (Zhang et al., 2021) and which shares structural similarities with human immunoglobulins (including interleukins) that can eventually produce immune dysregulation (Valcarcel et al., 2021). It is not still clear if all COVID-19 patients are equally susceptible to this ORF8-mediated immune dysregulation, but Down syndrome (Ds) patients with COVID-19 have more health complications, such as cardiac diseases, and higher rate of mortality than the general population, especially in those over 40 years old (Hüls et al., 2021). Ds is an important comorbidity since these patients have an extra copy of the TMPRSS2 gene, which probably produces enhanced levels of the transmembrane TMPRSS2 protease for S protein priming, facilitating the SARS-CoV-2 infection of the target cells (Hoffmann et al., 2020;De Toma and Dierssen, 2021).Therefore, we proposed a minimal mathematical model of the effect of the extra copy of TMPRSS2 on ORF8 production and persistence in the infected cells (Figure 1A), which reasonably fits with the experimental data reported in literature. According to the model results, we found that systemic levels of ORF8 are considerably higher and persists up to 40 days in patients with Ds (Figures 1B, C) in contrast with patients without Ds. These results support our hypothesis that the high susceptibility of people with Ds to be infected by SARS-CoV-2 is a consequence of the overproduction of TMPRSS2, which produces high systemic levels of ORF8 with the subsequent immune dysregulation, lung inflammatory effects, and cardiac damage that worsen the disease (Espinosa, 2020).Additional consequences of the overproduction of ORF8 in Ds patients with COVID-19 are as follows: 1) the several structural similarities of this viral protein with the nitric oxide synthase can alter the serum concentrations of NO, reducing the protective function of this gas against arrhythmias (Burger and Feng, 2011); 2) ORF8 can also be an important factor to aggravate the cytokine storm due its high degree of structural mimicry with immunoglobulins and their receptors (Valcarcel et al., 2021), with the subsequent small protoembolic events that cause a cardiovascular damage similar to that of older Ds patients never infected with Covid-19 (Colvin and Yeager, 2017; De Toma and Dierssen, 2020). 3) Taking into consideration that chromosome 21 also harbors multiple genes involved in the immune response, and their overexpression induces the dysregulation of interleukins IL-10, IL-22, and IL-26 prior to infection (De Weerd and Nguyen, 2020), the presence of high levels of ORF8 could also be an important factor to aggravate the cytokine storm in Ds patients with COVID-19.However, it is necessary to do more theoretical, experimental, and clinical research to elucidate the precise role of ORF8 in the immune dysregulation, lung inflammatory effects, and cardiac damage in this group of patients.

show abstract

“…Finally, Burger and Feng review current understanding and their own work on the protective role of NO in cardiac arrhythmia [7]. NO donors, nitroglycerin and sodium nitroprusside have long been known to protect the heart from ventricular arrhythmias [8,9].…”

mentioning

confidence: 99%

“…Additionally, genetic studies from animals deficient in NOS enzymes have found increased susceptibility to pharmacological or ischemiainduced arrhythmia while transgenic mice overexpressing certain NOS isozymes may be protected. The precise mechanisms of NO-mediated protection from arrhythmia are still under investigation but may include reductions in calcium overload, regulation of gap junction/connexin expression, reductions in oxidative stress, and regulation of sympathetic activity [7]. Further studies are required to determine the efficacy of specific NO donors and their effective doses before they can be tested in clinical trials in patients with cardiac arrhythmia.…”

mentioning

confidence: 99%

Editorial - Nitric Oxide, from its Chemistry to Biology and Disease

Feng¹

2011

TONOJ

View full text Add to dashboard Cite

Since the discovery of nitric oxide (NO) about 30 years ago, the field of NO research has been rapidly expanding and new aspects of NO chemistry and biology continue to emerge. Originally identified as a vasodilator, NO is now known to affect many biological processes from bacteria and single-celled eukaryotes to animals and humans. To share the latest development and to promote research on NO, the 6 th Canadian Nitric Oxide Society Conference was held in the beautiful campus of the University of Western Ontario, London, Ontario, Canada on June 10-11, 2010. A total of 50 people (principal investigators and their trainees) from ten universities came to the University of Western Ontario to present their latest work on NO. The research presented at this conference covered areas ranging from NO chemistry, biosynthesis, signal transduction, to the physiology and pharmacology of NO. This supplementary issue of The Open Nitric Oxide Journal publishes a selection of review articles on NO and gives a snap shot of the work presented at this conference.Nitric oxide synthase (NOS) is evolutionarily conserved and its origin can be traced back to bacteria, which have existed for more than three billion years. In the review by Rafferty [1], the structural similarities and differences between animal and bacterial NOS and how such differences may influence the extent and duration of bacterial NO production are examined. The roles of NO in microorganisms, which include protection against oxidative stress, UV damage and transcriptional regulation, are also discussed. An exciting development is the discovery of a NOS homologue in Naegleria gruberi, a single-celled, freeliving eukaryote. Further characterization of this NOS homologue may provide an important evolutionary link between bacteria and mammalian NOS. An important effect of NO is the post-translational modification of proteins through S-modification, which includesS-nitrosylation and S-glutathionylation. Identification of sites of S-modification in proteins is imperative in the understanding of the location, stability and frequency of these modifications. To this end, Faccenda and Mutus review the current methodologies available for identifying sites susceptible to S-modification and histochemical visualization of cellular compartments susceptible to S-modification [3]. The advantage and potential pitfalls of each method are outlined. In addition, factors that affect S-modification susceptibility are also discussed.The major function of the red blood cell (RBC) is to supply oxygen to demanding tissues and organs. To achieve this, it is now clear that the RBC itself also regulates blood flow and increases the number of oxygen-carrying cells to the hypoxic tissue. However, the mechanisms by which the RBC facilitates blood flow are not completely understood. Halpin et al. review information pertaining to the role of the RBC as both a deliverer of NO, and a stimulator of NO release via generation of ATP [4]. In addition, an evaluation of the potential downstream effects of RB...

show abstract

Protective Role of Nitric Oxide Against Cardiac Arrhythmia - An Update

Cited by 4 publications

References 128 publications

Protective Effects of Dinitrosyl Iron Complexes under Oxidative Stress in the Heart

Protective Effects of Dinitrosyl Iron Complexes under Oxidative Stress in the Heart

ORF8 and Health Complications of COVID-19 in Down Syndrome Patients

Editorial - Nitric Oxide, from its Chemistry to Biology and Disease

Contact Info

Product

Resources

About