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 [PIP(3)]), 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.

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

GHIGO, Alessandra;MORELLO, Fulvio;PERINO, Alessia;DAMILANO, Federico;HIRSCH, Emilio
2011

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 [PIP(3)]), 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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http://dx.doi.org/10.1007/s11897-011-0059-3
Phosphoinositide 3 kinase; PI3K; PI3K isoform; PI3Kα; PI3Kγ; PIP3; Cardiac pathophysiology; Hypertrophy; Contractility; Inflammation; β-adrenergic receptors; Heart failure; Myocardial infarction
Ghigo A; Morello F; Perino A; Damilano F; Hirsch E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/88965
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