edoc

Cardiac mTOR complex 2 preserves ventricular function in pressure-overload hypertrophy

Shende, Pankaj and Xu, Lifen and Morandi, Christian and Pentassuglia, Laura and Heim, Philippe and Lebboukh, Sonia and Berthonneche, Corinne and Pedrazzini, Thierry and Kaufmann, Beat A. and Hall, Michael N. and Rüegg, Markus A. and Brink, Marijke. (2016) Cardiac mTOR complex 2 preserves ventricular function in pressure-overload hypertrophy. Cardiovascular Research, 109 (1). pp. 103-114.

[img] PDF - Published Version
Restricted to Repository staff only until 1 January 2020.

981Kb

Official URL: http://edoc.unibas.ch/40862/

Downloads: Statistics Overview

Abstract

Mammalian target of rapamycin (mTOR), a central regulator of growth and metabolism, has tissue-specific functions depending on whether it is part of mTOR complex 1 (mTORC1) or mTORC2. We have previously shown that mTORC1 is required for adaptive cardiac hypertrophy and maintenance of function under basal and pressure-overload conditions. In the present study, we aimed to identify functions of mTORC2 in the heart.; Using tamoxifen-inducible cardiomyocyte-specific gene deletion, we generated mice deficient for cardiac rapamycin-insensitive companion of mTOR (rictor), an essential and specific component of mTORC2. Under basal conditions, rictor deficiency did not affect cardiac growth and function in young mice and also had no effects in adult mice. However, transverse aortic constriction caused dysfunction in the rictor-deficient hearts, whereas function was maintained in controls after 1 week of pressure overload. Adaptive increases in cardiac weight and cardiomyocyte cross-sectional area, fibrosis, and hypertrophic and metabolic gene expression were not different between the rictor-deficient and control mice. In control mice, maintained function was associated with increased protein levels of rictor, protein kinase C (PKC)βII, and PKCδ, whereas rictor ablation abolished these increases. Rictor deletion also significantly decreased PKCε at baseline and after pressure overload. Our data suggest that reduced PKCε and the inability to increase PKCβII and PKCδ abundance are, in accordance with their known function, responsible for decreased contractile performance of the rictor-deficient hearts.; Our study demonstrates that mTORC2 is implicated in maintaining contractile function of the pressure-overloaded male mouse heart.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Hall, Michael N. and Rüegg, Markus A. and Kaufmann, Beat and Brink, Marijke
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0008-6363
e-ISSN:1755-3245
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:20 Nov 2017 11:30
Deposited On:26 Jan 2016 08:01

Repository Staff Only: item control page