Key result
Methamphetamine caused right ventricular hypertrophy and increased expression of hypertrophic genes in female mice, but not in males, independent of right ventricular systolic pressure.
Why the study?
The mechanisms driving the increased prevalence and severity of methamphetamine-induced pulmonary arterial hypertension in females remain unclear.
Does methamphetamine treatment induce sex-dependent right ventricular hypertrophy and gene expression changes in mice?
Does methamphetamine treatment induce sex-dependent right ventricular hypertrophy and gene expression changes in mice?
Methamphetamine induces right ventricular hypertrophy and hypertrophic gene expression in female but not male mice, independent of pulmonary pressure changes, potentially explaining worse outcomes in female patients with MA-associated PAH.
MA-related RV gene changes in females merit targeted study; leaves open mechanistic drivers of sex-specific PAH risk.
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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Labazi et al. (2021) studied Methamphetamine-induced right ventricular hypertrophy. Methamphetamine vs. Vehicle was evaluated on Right and left ventricular systolic pressures, right ventricular hypertrophy, and gene expression. Methamphetamine caused right ventricular hypertrophy and increased expression of hypertrophic genes in female mice, but not in males, independent of right ventricular systolic pressure.
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