title: Specific PI3K isoform modulation in heart failure: lessons from transgenic mice.
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.
authors.affiliation: Molecular Biotechnology Center, University of Torino, Via Nizza 52, 10126, Torino, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ghigo
authors.forename: Fulvio
authors.initials: F
authors.lastname: Morello
authors.forename: Alessia
authors.initials: A
authors.lastname: Perino
authors.forename: Federico
authors.initials: F
authors.lastname: Damilano
authors.forename: Emilio
authors.initials: E
authors.lastname: Hirsch
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011943:Receptors, Adrenergic, beta; D019869:Phosphatidylinositol 3-Kinases