Lack of Contribution of p66shc to Pressure Overload-Induced Right Heart Hypertrophy |
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| Authors: | Christine Hirschh user,Akylbek Sydykov,Annemarie Wolf,Azadeh Esfandiary,Julia Bornbaum,Hanna Sarah Kutsche,Kerstin Boengler,Natascha Sommer,Rolf Schreckenberg,Klaus-Dieter Schlü ter,Norbert Weissmann,Ralph Schermuly,Rainer Schulz |
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| Affiliation: | 1.Physiologisches Institut, Justus-Liebig-Universität, 35392 Gießen, Germany; (A.W.); (J.B.); (H.S.K.); (K.B.); (R.S.); (K.-D.S.); (R.S.);2.Excellence Cluster Cardiopulmonary System (ECCPS), Justus-Liebig-Universität, 35392 Gießen, Germany; (A.S.); (A.E.); (N.S.); (N.W.); (R.S.) |
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| Abstract: | 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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| Keywords: | reactive oxygen species cardiac hypertrophy p66shc heart failure |
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