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Downregulation and nuclear relocation of MLP during the progression of right ventricular hypertrophy induced by chronic pressure overload.

Authors: Ecarnot-Laubriet, A  De Luca, K  Vandroux, D  Moisant, M  Bernard, C  Assem, M  Rochette, L  Teyssier, JR 
Citation: Ecarnot-Laubriet A, etal., J Mol Cell Cardiol. 2000 Dec;32(12):2385-95.
Pubmed: (View Article at PubMed) PMID:11113014
DOI: Full-text: DOI:10.1006/jmcc.2000.1269

The cardiac LIM domain protein MLP plays a crucial role in the architecture and mechanical function of cardiac myocytes. Mice lacking the MLP gene develop cardiac hypertrophy, dilated cardiopathy and heart failure. We investigated whether downregulation of MLP is induced by pressure overload and contributes to the physiopathology of cardiac hypertrophy and failure. We studied this mechanism in rat right ventricles submitted to pulmonary arterial hypertension, because it is known that this ventricle is very vulnerable to the deleterious effects of pressure overload. During the progression of cardiac hypertrophy to failure over a 31 days period there was a dramatic decrease by 50% of the MLP transcripts level. Consistently, immunohistochemistry detected very weak protein signals in the cytoplasms of cardiomyocytes at the failing stage, but myocytes nuclei were heavily labeled. The nuclear relocation was confirmed by the immunodetection of MLP on the nuclear and cytosolic fractions. This nuclear localization is the hallmark of a retro-differentiated phenotype, since it has been observed only in differentiating myoblasts. These changes were associated with ultrastructural disorganization of the myofibrils similar to that observed in MLP -/- mice. Therefore, MLP dowregulation occurring during gene reprogramming may critically contribute to mechanical failure of the myocardium.

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CRRD Object Information
CRRD ID: 1598503
Created: 2006-12-01
Species: All species
Last Modified: 2006-12-01
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.