Melusin, a muscle-specific integrin beta1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload
| Autor: | Roberta Poulet, Giuseppe Lembo, Luigi Fratta, Antonella Notte, Simona Guazzone, Emilio Hirsch, Guido Tarone, Marika De Acetis, Gennaro Marino, Fiorella Altruda, Carmine Vecchione, Lorenzo Silengo, Mara Brancaccio |
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| Rok vydání: | 2002 |
| Předmět: |
Mechanical overload
Male Cardiac output medicine.medical_specialty Heart Ventricles Cardiac Output Low Hemodynamics Muscle Proteins Cardiomegaly Biology General Biochemistry Genetics and Molecular Biology Aortic Coarctation Mice Phenylephrine Internal medicine insufficienza cardiaca medicine Animals Vasoconstrictor Agents Ventricular Function Gene Silencing Muscle Skeletal melusina trasduzione del segnale Pressure overload Mice Knockout Angiotensin II Integrin beta1 Myocardium Dilated cardiomyopathy General Medicine medicine.disease Biomechanical Phenomena Cytoskeletal Proteins Endocrinology Echocardiography Heart failure Cardiology Female Stress Mechanical Carrier Proteins medicine.drug Signal Transduction |
| Zdroj: | Nature medicine. 9(1) |
| ISSN: | 1078-8956 |
| Popis: | Cardiac hypertrophy is an adaptive response to a variety of mechanical and hormonal stimuli, and represents an early event in the clinical course leading to heart failure. By gene inactivation, we demonstrate here a crucial role of melusin, a muscle-specific protein that interacts with the integrin beta1 cytoplasmic domain, in the hypertrophic response to mechanical overload. Melusin-null mice showed normal cardiac structure and function in physiological conditions, but when subjected to pressure overload--a condition that induces a hypertrophic response in wild-type controls--they developed an abnormal cardiac remodeling that evolved into dilated cardiomyopathy and contractile dysfunction. In contrast, the hypertrophic response was identical in wild-type and melusin-null mice after chronic administration of angiotensin II or phenylephrine at doses that do not increase blood pressure--that is, in the absence of cardiac biomechanical stress. Analysis of intracellular signaling events induced by pressure overload indicated that phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) was specifically blunted in melusin-null hearts. Thus, melusin prevents cardiac dilation during chronic pressure overload by specifically sensing mechanical stress. |
| Databáze: | OpenAIRE |
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