| | |  | | | | Record from Web of Science® | | | | | | |
| Melusin, a muscle-specific integrin beta(1)-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload |
|
|
| Author(s): Brancaccio M, Fratta L, Notte A, Hirsch E, Poulet R, Guazzone S, De Acetis M, Vecchione C, Marino G, Altruda F, Silengo L, Tarone G, Lembo G |
| Source: NATURE MEDICINE Volume: 9 Issue: 1 Pages: 68-75 Published: JAN 2003 |
| Times Cited: 109 References: 42 |
| Abstract: 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 1 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 wildtype 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Tarone, G (reprint author), Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy |
Addresses:
1. Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy
2. IRCCS Neuromed, Dept Angiocardioneurol, I-86077 Pozzilli, IS Italy
3. San Giovanni Battista Hosp, Expt Med Res Ctr, I-10126 Turin, Italy
4. Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy |
| Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: 632EC |
| ISSN: 1078-8956 |
| DOI: 10.1038/nm805 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |