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Specific PI3K Isoform Modulation in Heart Failure: Lessons from Transgenic Mice

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Abstract

Cardiac pathophysiology heavily relies on receptor-mediated signal transduction, and pharmacologic control of such biological processes has proven successful in preventing and treating multiple heart diseases. Recent progress in the study of receptor-mediated signal transduction events in the heart highlighted the role of a family of lipid kinases known as phosphoinositide 3-kinases (PI3Ks). These enzymes are involved downstream different receptors in the production of a lipid second messenger molecule (namely phosphatidylinositol (3,4,5)-trisphosphate [PIP3]), which mediates a large number of biological responses critical for the heart, including cardiomyocyte growth, survival, and contractility as well as cardiovascular inflammation. This review focuses on the recent advances in the understanding of PI3K function in cardiac pathophysiology obtained by studying mouse mutants for different PI3K genes and by validating the effects of PI3K pharmacologic inhibition in preclinical models of critical cardiac diseases like heart failure.

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Acknowledgments

Drs. Alessandra Ghigo, Fulvio Morello, and Alessia Perino contributed equally to this manuscript.

Disclosures

Drs. Alessandra Ghigo, Fulvio Morello, Alessia Perino, Federico Damilano, and Emilio Hirsch all have received a grant from EUGeneHeart and have grants pending from Fondation Leducq.

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Authors and Affiliations

  1. Molecular Biotechnology Center, University of Torino, Via Nizza 52, 10126, Torino, Italy

    Alessandra Ghigo, Fulvio Morello, Alessia Perino, Federico Damilano & Emilio Hirsch

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  1. Alessandra Ghigo
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  2. Fulvio Morello
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  3. Alessia Perino
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  4. Federico Damilano
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Correspondence to Emilio Hirsch.

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Ghigo, A., Morello, F., Perino, A. et al. Specific PI3K Isoform Modulation in Heart Failure: Lessons from Transgenic Mice. Curr Heart Fail Rep 8, 168–175 (2011). https://doi.org/10.1007/s11897-011-0059-3

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