Key result
p66shc deletion fails to prevent right ventricular hypertrophy or failure in pressure overload.
Why the study?
The hydrogen peroxide-generating protein p66shc has been linked to LV hypertrophy, but its role in RV hypertrophy and progression to RV failure remains unclear.
Does genetic deletion of p66shc prevent right ventricular hypertrophy and failure in a mouse model of pulmonary artery banding?
Does genetic deletion of p66shc prevent right ventricular hypertrophy and failure in a mouse model of pulmonary artery banding?
Unlike its protective role in left ventricular hypertrophy, the deletion of p66shc does not mitigate pressure overload-induced right ventricular hypertrophy or failure.
Answers are grounded in this paper and cite their sources.
Contrasts with left ventricular protection; leaves open ventricle-specific p66shc roles in pressure-overload remodeling.
The leading cause of death in pulmonary arterial hypertension (PAH) is right ventricular (RV) failure (RVF). Reactive oxygen species (ROS) have been suggested to play a role in the development of RV hypertrophy (RVH) and the transition to RVF. The hydrogen peroxide-generating protein p66shc has been associated with left ventricular (LV) hypertrophy but its role in RVH is unclear. The purpose of this study was to determine whether genetic deletion of p66shc affects the development and/or progression of RVH and RVF in the pulmonary artery banding (PAB) model of RV pressure overload. The impact of p66shc on mitochondrial ROS formation, RV cardiomyocyte function, as well as on RV morphology and function were studied three weeks after PAB or sham operation. PAB in wild type mice did not affect mitochondrial ROS production or RV cardiomyocyte function, but induced RVH and impaired cardiac function. Genetic deletion of p66shc did also not alter basal mitochondrial ROS production or RV cardiomyocyte function, but impaired RV cardiomyocyte shortening was observed following PAB. The development of RVH and RVF following PAB was not affected by p66shc deletion. Thus, our data suggest that p66shc-derived ROS are not involved in the development and progression of RVH or RVF in PAH.
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Hirschhäuser et al. (2020) studied Right ventricular hypertrophy and right ventricular failure (n=64). Genetic deletion of p66shc vs. Wild-type was evaluated on Development of right ventricular hypertrophy and right ventricular failure 3 weeks after pulmonary artery banding. Genetic deletion of p66shc did not affect the development and progression of right ventricular hypertrophy or right ventricular failure in a mouse model of pressure overload induced by pulmonary artery banding.
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