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Life
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Nitric Oxide Metabolites as Biomarkers of Cardiovascular Diseases
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Nitric Oxide Metabolites as Biomarkers of Cardiovascular Diseases

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 3202

Special Issue Editors

Dr. Nadezhda G. Gumanova

E-Mail Website
Guest Editor
National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia
Interests: atherosclerosis; nitric oxide; biomarkers; nitrate
Dr. Alexander Kots

E-Mail Website
Guest Editor
Department of Veteran Affairs, Veteran Affairs Palo Alto Health Care Services, VAPAHCS, Palo Alto, CA, USA
Interests: nitric oxide; cyclic GMP; nitrate; cardiovascular diseases

Special Issue Information

Dear Colleagues,

Nitric oxide (NO) is an important signaling molecule produced endogenously in the body by specific enzymes or during various redox reactions. NO is involved in various mechanisms, regulating vascular tone and blood pressure, the immune system, and neuronal signal transduction. NO is a free radical and is unstable under physiological conditions. NO is usually oxidized to form nitrite and nitrate and reacts with other free radicals, metal ions, or redox-active groups to form peroxynitrite, nitrosyl complexes, S-nitrosothiols, or other stable metabolites. These reactions are influenced by oxidative and metabolic stress and other pathological conditions.

Various cardiovascular diseases, especially atherosclerosis, have a complex pathogenesis, development, and outcomes in patients, as defined by a combination of genetic, environmental, and behavioral characteristics at individual and population levels. The correct stratification of patients with cardiovascular diseases usually requires an ensemble of rigorously defined biomarkers linked to pathogenesis with predictable power to obtain specific outcomes. NO is one of the main messenger molecules linked to the changes in vascular biology, oxidative stress, and the genetic, regulatory, and metabolic factors that are characteristic of various cardiovascular diseases. Thus, stable NO metabolites may represent important and mechanistically relevant biomarkers for pathologies of the cardiovascular system.

Recent clinical studies demonstrated that certain NO metabolites, including nitrate, nitrite, nitrotyrosine, S-nitrosothiols, and other species, are associated with pathogenesis, development, and outcomes in patients with cardiovascular disorders.

This Special Issue will collect original basic and clinical research and reviews on the diagnostic and prognostic value of NO metabolites as biomarkers of cardiovascular diseases to enhance patient stratification and provide assistance in the development of novel treatment strategies.

Dr. Nadezhda G. Gumanova
Dr. Alexander Kots
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nitric oxide
  • nitrotyrosine
  • nitrate
  • cardiovascular diseases
  • mortality
  • 8-nitroguanine
  • nitrite
  • nitrosylation
  • clinical biomarkers

Published Papers (2 papers)

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Research

19 pages, 747 KiB  
Article
VAERS Vasculitis Adverse Events Retrospective Study: Etiology Model of Immune Complexes Activating Fc Receptors in Kawasaki Disease and Multisystem Inflammatory Syndromes
by Darrell O. Ricke and Nora Smith
Life 2024, 14(3), 353; https://doi.org/10.3390/life14030353 - 7 Mar 2024
Cited by 1 | Viewed by 1603
Abstract
Background: Vasculitis diseases include Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), Multisystem Inflammatory Syndrome (MIS), Henoch–Schönlein purpura (HS), or IgA vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than [...] Read more.
Background: Vasculitis diseases include Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), Multisystem Inflammatory Syndrome (MIS), Henoch–Schönlein purpura (HS), or IgA vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than in adults. These diseases have been extensively studied, but understanding of the disease etiology remains to be established. Objective: Many studies have failed to demonstrate an association between vasculitis diseases and vaccination; this study examines possible associations. Methods: Herein, the Vaccine Adverse Event Reporting System (VAERS) database is retrospectively examined for associations between vasculitis diseases and immunizations. Results: For some vaccines, the number of rare cases of KD, MIS, and HS are higher than the background rates. These rare cases are predicted to occur in individuals with (1) genetic risk factors with (2) antibody titer levels above the primary immune response level. Herein, the model of humoral immune response antibodies bound to antigens (pathogen or vaccine) creating immune complexes is proposed. These immune complexes are proposed to bind Fc receptors on immune cells and platelets, resulting in cell activation and the release of inflammatory molecules including histamine and serotonin. Immune complexes and inflammatory molecules including serotonin and histamine likely trigger vasculitis. Elevated serotonin and possibly histamine drive initial vasoconstrictions, disrupting blood flow. Increased blood flow pressure from cardiac capillary vasoconstrictions is predicted to trigger coronary artery aneurysms (CAA) or lesions (CAL) in some patients. For KDSS and MIS patients, these cardiac capillary vasoconstrictions are predicted to result in ischemia followed by ventricular dysfunction. Ongoing ischemia can result in long-term cardiac damage. Cases associated with pathogens are likely to have persistent infections triggering disease onset. Conclusion: The proposed model of immune complexes driving disease initial disease etiology by Fc receptor activation of immune cells and platelets, resulting in elevated histamine and serotonin levels, is testable and is consistent with disease symptoms and current treatments. Full article
(This article belongs to the Special Issue Nitric Oxide Metabolites as Biomarkers of Cardiovascular Diseases)
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15 pages, 2378 KiB  
Article
6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart
by José Britto-Júnior, Lincoln Rangel Medeiros-Teixeira, Antonio Tiago Lima, Letícia Costa Dassow, Rodrigo Álvaro Brandão Lopes-Martins, Rafael Campos, Manoel Odorico Moraes, Maria Elisabete A. Moraes, Edson Antunes and Gilberto De Nucci
Life 2023, 13(10), 2012; https://doi.org/10.3390/life13102012 - 4 Oct 2023
Cited by 3 | Viewed by 1191
Abstract
Background: 6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether 6-nitrodopamine is released from rat isolated ventricles (RIV) and modulates heart inotropism. Methods: Catecholamines released from RIV were quantified by [...] Read more.
Background: 6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether 6-nitrodopamine is released from rat isolated ventricles (RIV) and modulates heart inotropism. Methods: Catecholamines released from RIV were quantified by LC-MS/MS and their effects on heart inotropism were evaluated by measuring left ventricular developed pressure (LVDP) in Langendorff’s preparation. Results: 6-nitrodopamine was the major released catecholamine from RIV. Incubation with L-NAME (100 µM), but not with tetrodotoxin (1 µM), caused a significant reduction in 6-nitrodopamine basal release. 6-nitrodopamine release was significantly reduced in ventricles obtained from L-NAME chronically treated animals. 6-nitrodopamine (0.01 pmol) caused significant increases in LVDP and dP/dtmax, whereas dopamine and noradrenaline required 10 pmol, and adrenaline required 100 pmol, to induce similar increases in LVDP and dP/dtmax. The infusion of atenolol (10 nM) reduced basal LVDP and blocked the increases in LVDP induced by 6-ND (0.01 pmol), without affecting the increases in LVDP induced by 10 nmol of dopamine and noradrenaline and that induced by adrenaline (100 nmol). Conclusions: 6-nitrodopamine is the major catecholamine released from rat isolated ventricles. It is 1000 times more potent than dopamine and noradrenaline and is selectively blocked by atenolol, indicating that 6-ND is a main regulator of heart inotropism. Full article
(This article belongs to the Special Issue Nitric Oxide Metabolites as Biomarkers of Cardiovascular Diseases)
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