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Current status of NADPH oxidase research in cardiovascular pharmacology
The implications of reactive oxygen species in cardiovascular disease have been known for some decades. Rationally, therapeutic antioxidant strategies combating oxidative stress have been developed, but the results of clinical trials have not been as good as expected. Therefore, to move forward in t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750863/ https://www.ncbi.nlm.nih.gov/pubmed/23983473 http://dx.doi.org/10.2147/VHRM.S33053 |
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author | Rodiño-Janeiro, Bruno K Paradela-Dobarro, Beatriz Castiñeiras-Landeira, María Isabel Raposeiras-Roubín, Sergio González-Juanatey, José R Álvarez, Ezequiel |
author_facet | Rodiño-Janeiro, Bruno K Paradela-Dobarro, Beatriz Castiñeiras-Landeira, María Isabel Raposeiras-Roubín, Sergio González-Juanatey, José R Álvarez, Ezequiel |
author_sort | Rodiño-Janeiro, Bruno K |
collection | PubMed |
description | The implications of reactive oxygen species in cardiovascular disease have been known for some decades. Rationally, therapeutic antioxidant strategies combating oxidative stress have been developed, but the results of clinical trials have not been as good as expected. Therefore, to move forward in the design of new therapeutic strategies for cardiovascular disease based on prevention of production of reactive oxygen species, steps must be taken on two fronts, ie, comprehension of reduction-oxidation signaling pathways and the pathophysiologic roles of reactive oxygen species, and development of new, less toxic, and more selective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors, to clarify both the role of each NADPH oxidase isoform and their utility in clinical practice. In this review, we analyze the value of NADPH oxidase as a therapeutic target for cardiovascular disease and the old and new pharmacologic agents or strategies to prevent NADPH oxidase activity. Some inhibitors and different direct or indirect approaches are available. Regarding direct NADPH oxidase inhibition, the specificity of NADPH oxidase is the focus of current investigations, whereas the chemical structure-activity relationship studies of known inhibitors have provided pharmacophore models with which to search for new molecules. From a general point of view, small-molecule inhibitors are preferred because of their hydrosolubility and oral bioavailability. However, other possibilities are not closed, with peptide inhibitors or monoclonal antibodies against NADPH oxidase isoforms continuing to be under investigation as well as the ongoing search for naturally occurring compounds. Likewise, some different approaches include inhibition of assembly of the NADPH oxidase complex, subcellular translocation, post-transductional modifications, calcium entry/release, electron transfer, and genetic expression. High-throughput screens for any of these activities could provide new inhibitors. All this knowledge and the research presently underway will likely result in development of new drugs for inhibition of NADPH oxidase and application of therapeutic approaches based on their action, for the treatment of cardiovascular disease in the next few years. |
format | Online Article Text |
id | pubmed-3750863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-37508632013-08-27 Current status of NADPH oxidase research in cardiovascular pharmacology Rodiño-Janeiro, Bruno K Paradela-Dobarro, Beatriz Castiñeiras-Landeira, María Isabel Raposeiras-Roubín, Sergio González-Juanatey, José R Álvarez, Ezequiel Vasc Health Risk Manag Review The implications of reactive oxygen species in cardiovascular disease have been known for some decades. Rationally, therapeutic antioxidant strategies combating oxidative stress have been developed, but the results of clinical trials have not been as good as expected. Therefore, to move forward in the design of new therapeutic strategies for cardiovascular disease based on prevention of production of reactive oxygen species, steps must be taken on two fronts, ie, comprehension of reduction-oxidation signaling pathways and the pathophysiologic roles of reactive oxygen species, and development of new, less toxic, and more selective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors, to clarify both the role of each NADPH oxidase isoform and their utility in clinical practice. In this review, we analyze the value of NADPH oxidase as a therapeutic target for cardiovascular disease and the old and new pharmacologic agents or strategies to prevent NADPH oxidase activity. Some inhibitors and different direct or indirect approaches are available. Regarding direct NADPH oxidase inhibition, the specificity of NADPH oxidase is the focus of current investigations, whereas the chemical structure-activity relationship studies of known inhibitors have provided pharmacophore models with which to search for new molecules. From a general point of view, small-molecule inhibitors are preferred because of their hydrosolubility and oral bioavailability. However, other possibilities are not closed, with peptide inhibitors or monoclonal antibodies against NADPH oxidase isoforms continuing to be under investigation as well as the ongoing search for naturally occurring compounds. Likewise, some different approaches include inhibition of assembly of the NADPH oxidase complex, subcellular translocation, post-transductional modifications, calcium entry/release, electron transfer, and genetic expression. High-throughput screens for any of these activities could provide new inhibitors. All this knowledge and the research presently underway will likely result in development of new drugs for inhibition of NADPH oxidase and application of therapeutic approaches based on their action, for the treatment of cardiovascular disease in the next few years. Dove Medical Press 2013 2013-07-25 /pmc/articles/PMC3750863/ /pubmed/23983473 http://dx.doi.org/10.2147/VHRM.S33053 Text en © 2013 Rodiño-Janeiro et al, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Review Rodiño-Janeiro, Bruno K Paradela-Dobarro, Beatriz Castiñeiras-Landeira, María Isabel Raposeiras-Roubín, Sergio González-Juanatey, José R Álvarez, Ezequiel Current status of NADPH oxidase research in cardiovascular pharmacology |
title | Current status of NADPH oxidase research in cardiovascular
pharmacology |
title_full | Current status of NADPH oxidase research in cardiovascular
pharmacology |
title_fullStr | Current status of NADPH oxidase research in cardiovascular
pharmacology |
title_full_unstemmed | Current status of NADPH oxidase research in cardiovascular
pharmacology |
title_short | Current status of NADPH oxidase research in cardiovascular
pharmacology |
title_sort | current status of nadph oxidase research in cardiovascular
pharmacology |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750863/ https://www.ncbi.nlm.nih.gov/pubmed/23983473 http://dx.doi.org/10.2147/VHRM.S33053 |
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