Phosphoinositide 3-kinase gamma controls inflammation-induced myocardial depression via sequential cAMP and iNOS signalling

Cardiovascular Research
Bernadin Ndongson-DongmoReinhard Bauer

Abstract

Sepsis-induced myocardial depression (SIMD), an early and frequent event of infection-induced systemic inflammatory response syndrome (SIRS), is characterized by reduced contractility irrespective of enhanced adrenergic stimulation. Phosphoinositide-3 kinase γ (PI3Kγ) is known to prevent β-adrenergic overstimulation via its scaffold function by activating major cardiac phosphodiesterases and restricting cAMP levels. However, the role of PI3Kγ in SIRS-induced myocardial depression is unknown. This study is aimed at determining the specific role of lipid kinase-dependent and -independent functions of PI3Kγ in the pathogenesis of SIRS-induced myocardial depression. PI3Kγ knockout mice (PI3Kγ(-/-)), mice expressing catalytically inactive PI3Kγ (PI3Kγ(KD/KD)), and wild-type mice (P3Kγ(+/+)) were exposed to lipopolysaccharide (LPS)-induced systemic inflammation and assessed for survival, cardiac autonomic nervous system function, and left ventricular performance. Additionally, primary adult cardiomyocytes were used to analyse PI3Kγ effects on myocardial contractility and inflammatory response. SIRS-induced adrenergic overstimulation induced a transient hypercontractility state in PI3Kγ(-/-) mice, followed by reduced contractility. In...Continue Reading

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Citations

Dec 16, 2016·American Journal of Physiology. Cell Physiology·Kedar GhimireJeffrey S Isenberg
Apr 25, 2019·Basic Research in Cardiology·Bernadin Ndongson-DongmoReinhard Bauer
Sep 5, 2019·Biomolecules·Bernd Nürnberg, Sandra Beer-Hammer
Dec 8, 2017·Phytotherapy Research : PTR·Nan ZhangQi-Zhu Tang
May 12, 2018·International Journal of Molecular Medicine·Qiancheng LuoMingming Jin
Jun 3, 2020·Journal of Cell Science·Adrien LupieriMuriel Laffargue
Apr 4, 2021·International Journal of Molecular Sciences·Trim LajqiReinhard Bauer

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