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

Labazi, Hicham and Nilsen, Margaret and MacLean, Margaret R. (2021) Sex-dependent right ventricular hypertrophic gene changes after methamphetamine treatment in mice. European Journal of Pharmacology, 900. 174066. ISSN 0014-2999 (https://doi.org/10.1016/j.ejphar.2021.174066)

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Abstract

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.

  • Item type:Article
    ID code:76007
    Dates:
    Date
    Event
    5 June 2021
    Published
    28 March 2021
    Published Online
    22 March 2021
    Accepted
    Keywords:methamphetamine, pulmonary arterial hypertension, right ventricular hypertrophy, sexual dimorphism, Pharmacy and materia medica, Pharmacology
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:01 Apr 2021 15:39
    Last modified:03 Nov 2021 01:58
    URI:https://strathprints.strath.ac.uk/id/eprint/76007
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