| First Author | Brancaccio M | Year | 2003 |
| Journal | Nat Med | Volume | 9 |
| Issue | 1 | Pages | 68-75 |
| PubMed ID | 12496958 | Mgi Jnum | J:81163 |
| Mgi Id | MGI:2448192 | Doi | 10.1038/nm805 |
| Citation | Brancaccio M, et al. (2003) Melusin, a muscle-specific integrin beta(1)-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload. Nat Med 9(1):68-75 |
| abstractText | 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 beta(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 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. |
