title: Integrin signalling: the tug-of-war in heart hypertrophy.
abstract: The mechanical stress imposed by hemodynamic overload on heart walls is a primary event in triggering the cardiac hypertrophic response. Integrins, a class of membrane receptors, are major players in transmitting the mechanical force across the plasma membrane and sensing the mechanical load in cardiomyocytes. In fact, integrins, together with a number of associated cytoskeletal proteins, connect the sarcomeric contractile apparatus to the extracellular matrix across the plasma membrane and trigger intracellular signaling pathways activating the cardiomyocyte hypertrophy program. In this review, we will discuss the role of the muscle-specific integrin isoform beta1D and of associated proteins such as FAK, melusin, vinculin, zyxin, VASP, and migfilin that are the most upstream elements ("initiators") activated by mechanical strain. These molecules trigger a coordinated downstream signaling cascade involving proteins such as AKT, RAS, and MAPKs that execute the biochemical program leading to cardiomyocyte hypertrophy. Better understanding of the functional role of the initiator elements is of key importance to developing novel strategies to control cardiac hypertrophy and prevent heart failure.
authors.affiliation: Department of Genetics, Biology, and Biochemistry, Turin University, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Brancaccio
authors.forename: Emilio
authors.initials: E
authors.lastname: Hirsch
authors.forename: Antonella
authors.initials: A
authors.lastname: Notte
authors.forename: Giulio
authors.initials: G
authors.lastname: Selvetella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lembo
authors.forename: Guido
authors.initials: G
authors.lastname: Tarone
mesh_terms: D000199:Actins / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; C492400:ITGB1BP2 protein, human; D016023:Integrins; D009124:Muscle Proteins; D051417:Focal Adhesion Kinase 1