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Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy
Probenecid has been used for decades in the treatment of gout but recently has also been found to improve outcomes in patients with heart failure via stimulation of the transient receptor potential vanilloid 2 (TRPV2) channel in cardiomyocytes. This study tested the use of probenecid on a novel mous...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100971/ https://www.ncbi.nlm.nih.gov/pubmed/32218573 http://dx.doi.org/10.1371/journal.pone.0230386 |
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author | Onusko, Evan McDermott, Michael R. Robbins, Nathan Liu, Guansheng Kranias, Evangelia G. Rubinstein, Jack Koch, Sheryl E. |
author_facet | Onusko, Evan McDermott, Michael R. Robbins, Nathan Liu, Guansheng Kranias, Evangelia G. Rubinstein, Jack Koch, Sheryl E. |
author_sort | Onusko, Evan |
collection | PubMed |
description | Probenecid has been used for decades in the treatment of gout but recently has also been found to improve outcomes in patients with heart failure via stimulation of the transient receptor potential vanilloid 2 (TRPV2) channel in cardiomyocytes. This study tested the use of probenecid on a novel mouse model of peripartum cardiomyopathy (PPCM) as a potential treatment option. A human mutation of the human heat shock protein 20 (Hsp20-S10F) in mice has been recently shown to result in cardiomyopathy, when exposed to pregnancies. Treatment with either probenecid or control sucrose water was initiated after the first pregnancy in both wild type and Hsp20-S10F mice. Serial echocardiography was performed during subsequent pregnancies and hearts were collected after the third pregnancies for staining and molecular analysis. Hsp20-S10F mice treated with probenecid had decreased mortality, hypertrophy, TRPV2 expression and molecular parameters of heart failure. Probenecid treatment also decreased apoptosis as evidenced by an increase in the level of Bcl-2/Bax. Probenecid improved survival in a novel mouse model of PPCM and may be an appropriate therapy for humans with PPCM as it has a proven safety and tolerability in patients with heart failure. |
format | Online Article Text |
id | pubmed-7100971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-71009712020-04-03 Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy Onusko, Evan McDermott, Michael R. Robbins, Nathan Liu, Guansheng Kranias, Evangelia G. Rubinstein, Jack Koch, Sheryl E. PLoS One Research Article Probenecid has been used for decades in the treatment of gout but recently has also been found to improve outcomes in patients with heart failure via stimulation of the transient receptor potential vanilloid 2 (TRPV2) channel in cardiomyocytes. This study tested the use of probenecid on a novel mouse model of peripartum cardiomyopathy (PPCM) as a potential treatment option. A human mutation of the human heat shock protein 20 (Hsp20-S10F) in mice has been recently shown to result in cardiomyopathy, when exposed to pregnancies. Treatment with either probenecid or control sucrose water was initiated after the first pregnancy in both wild type and Hsp20-S10F mice. Serial echocardiography was performed during subsequent pregnancies and hearts were collected after the third pregnancies for staining and molecular analysis. Hsp20-S10F mice treated with probenecid had decreased mortality, hypertrophy, TRPV2 expression and molecular parameters of heart failure. Probenecid treatment also decreased apoptosis as evidenced by an increase in the level of Bcl-2/Bax. Probenecid improved survival in a novel mouse model of PPCM and may be an appropriate therapy for humans with PPCM as it has a proven safety and tolerability in patients with heart failure. Public Library of Science 2020-03-27 /pmc/articles/PMC7100971/ /pubmed/32218573 http://dx.doi.org/10.1371/journal.pone.0230386 Text en © 2020 Onusko et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Onusko, Evan McDermott, Michael R. Robbins, Nathan Liu, Guansheng Kranias, Evangelia G. Rubinstein, Jack Koch, Sheryl E. Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy |
title | Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy |
title_full | Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy |
title_fullStr | Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy |
title_full_unstemmed | Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy |
title_short | Probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy |
title_sort | probenecid treatment improves outcomes in a novel mouse model of peripartum cardiomyopathy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100971/ https://www.ncbi.nlm.nih.gov/pubmed/32218573 http://dx.doi.org/10.1371/journal.pone.0230386 |
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