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Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice

Methamphetamine (MA) abuse is associated with the development of pulmonary arterial hypertension (PAH) and subsequent right ventricular failure. A recent clinical study demonstrated that female sex is a major risk factor for MA-induced PAH. The mechanisms associated with increased prevalence and sev...

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Autores principales: Labazi, Hicham, Nilsen, Margaret, MacLean, Margaret R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111419/
https://www.ncbi.nlm.nih.gov/pubmed/33789156
http://dx.doi.org/10.1016/j.ejphar.2021.174066
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author Labazi, Hicham
Nilsen, Margaret
MacLean, Margaret R.
author_facet Labazi, Hicham
Nilsen, Margaret
MacLean, Margaret R.
author_sort Labazi, Hicham
collection PubMed
description Methamphetamine (MA) abuse is associated with the development of pulmonary arterial hypertension (PAH) and subsequent right ventricular failure. A recent clinical study demonstrated that female sex is a major risk factor for MA-induced PAH. The mechanisms associated with increased prevalence and severity of MA-induced PAH in females are still unclear. We hypothesized that MA may promote changes in gene expression in the right ventricle contributing to the development and/or worsening of PAH in females. Male and female C57BL/6 mice were treated with either MA or vehicle. Right and left ventricular systolic pressures (RVSP and LVSP, respectively) were assessed and tissue samples were collected for gene expression and histology. LVSP and RVSP were not affected by MA in either males or females. Right ventricular hypertrophy was significantly increased by MA in females but it was not affected by MA in males. In the female mice, MA-induced right ventricular hypertrophy was associated with increased expression of brain natriuretic peptide gene and members of the TGF-β receptor signaling pathway such as TGF-β receptor-1, smad3 and smad7. In male mice, there were no changes in right ventricular gene expression. Our results suggest that MA caused right ventricular hypertrophy in female mice, but not in males and that this was associated with an increase in hypertrophic genes. The right ventricular hypertrophy was not dependent on increased RVSP suggesting a direct effect of MA on the right ventricle. If this translates to PAH patients, it might explain the poor outcome observed in MA-associated female PAH patients.
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spelling pubmed-81114192021-06-05 Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice Labazi, Hicham Nilsen, Margaret MacLean, Margaret R. Eur J Pharmacol Full Length Article Methamphetamine (MA) abuse is associated with the development of pulmonary arterial hypertension (PAH) and subsequent right ventricular failure. A recent clinical study demonstrated that female sex is a major risk factor for MA-induced PAH. The mechanisms associated with increased prevalence and severity of MA-induced PAH in females are still unclear. We hypothesized that MA may promote changes in gene expression in the right ventricle contributing to the development and/or worsening of PAH in females. Male and female C57BL/6 mice were treated with either MA or vehicle. Right and left ventricular systolic pressures (RVSP and LVSP, respectively) were assessed and tissue samples were collected for gene expression and histology. LVSP and RVSP were not affected by MA in either males or females. Right ventricular hypertrophy was significantly increased by MA in females but it was not affected by MA in males. In the female mice, MA-induced right ventricular hypertrophy was associated with increased expression of brain natriuretic peptide gene and members of the TGF-β receptor signaling pathway such as TGF-β receptor-1, smad3 and smad7. In male mice, there were no changes in right ventricular gene expression. Our results suggest that MA caused right ventricular hypertrophy in female mice, but not in males and that this was associated with an increase in hypertrophic genes. The right ventricular hypertrophy was not dependent on increased RVSP suggesting a direct effect of MA on the right ventricle. If this translates to PAH patients, it might explain the poor outcome observed in MA-associated female PAH patients. Elsevier Science 2021-06-05 /pmc/articles/PMC8111419/ /pubmed/33789156 http://dx.doi.org/10.1016/j.ejphar.2021.174066 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Full Length Article
Labazi, Hicham
Nilsen, Margaret
MacLean, Margaret R.
Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice
title Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice
title_full Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice
title_fullStr Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice
title_full_unstemmed Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice
title_short Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice
title_sort sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111419/
https://www.ncbi.nlm.nih.gov/pubmed/33789156
http://dx.doi.org/10.1016/j.ejphar.2021.174066
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