Melusin protects from cardiac rupture and improves functional remodelling after myocardial infarction
Authors: Lars S Maier
Chantal Munts
Stefan Neef
Ali El-Armouche
Karin Sipido
Axel Kaul
Vera Regitz-Zagrosek
Jean Luc Balligand
Katrin Sch√§fer
Elke Detre
Caroline Bouzin
Federico Damilano
Ren√©e Ventura-Clapier
Anne Garnier
Ralph Kn√∂ll
Nana Maria Wagner
Guido Tarone
Tim Seidler
Mara Brancaccio
Johannes Vogt
Bernhard Uns√∂ld
Mauro Sbroggi√≤
Emilio Hirsch
Virginie Bito
Gerd Hasenfu√ü
Marc Van Bilsen
Thomas Eschenhagen
Carola Schubert
Annalen Bleckmann
Journal: Cardiovascular research (2014)
Discipline: CLINICAL MEDICINE
Keywords: Chaperon; Infarction; Map kinase; Remodelling; Transgenic animal models.
Affiliations: Department of Cardiology, University of G√∂ttingen, Heart Research Center G√∂ttingen, G√∂ttingen, Germany., Department of Cardiology, University of G√∂ttingen, Heart Research Center G√∂ttingen, G√∂ttingen, Germany, Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Universit√† di Torino, Turin, Italy, Institute of Gender in Medicine, Charit√©-Universit√§tsmedizin, Berlin, Germany, Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands, Division of Experimental Cardiology, Department of Cardiovascular Medicine, University of Leuven, Leuven, Belgium, Department of Hematology and Oncology, University of G√∂ttingen, G√∂ttingen, Germany, Pharmacology and Therapeutics, Institut de Recherche Exp√©rimentale et Clinique (IREC), Universit√© Catholique de Louvain, Brussels, Belgium, INSERM U-769, Ch√¢tenay-Malabry, France, Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg Eppendorf, Hamburg, Germany, Department of Pharmacology, University of G√∂ttingen, Heart Research Center G√∂ttingen, G√∂ttingen, Germany, Myocardial Genetics, Imperial College London, London, UK

Abstract:  Aims: Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach. Methods and results: Mice overexpressing melusin in the heart (TG) and wild-type controls (WT) were subjected to permanent LAD ligation and both the acute response (Day 3) and subsequent remodelling (2 weeks) were examined. Mortality in wild-type mice was significant between Days 3 and 7, primarily due to cardiac rupture, but melusin's overexpression strongly reduced mortality (43.2% in wild-type vs. 27.3% in melusin-TG, P = 0.005). At Day 3 after MI, a time point preceding the mortality peak, TG hearts had increased heat shock protein 70 expression, increased ERK1/2 signalling, reduced cardiomyocyte hyper-contractility and inflammatory cell infiltrates, and increased matricellular protein expression in the infarcted area. At 2 weeks after MI, melusin overexpression conferred a favourable adaptive remodelling characterized by reduced left ventricle dilatation and better preserved contractility in the presence of a comparable degree of hypertrophy. Adaptive remodelling in melusin TG mice was characterized by reduced apoptosis and fibrosis as well as increased cardiomyocyte contractility. Conclusions: Consistent with its function as a chaperone protein, melusin overexpression exerts a dual protective action following MI reducing an array of maladaptive processes. In the early phase after MI, reduced inflammation and myocyte remodelling protect against cardiac rupture. Chronically, reduced myocyte loss and matrix remodelling, with preserved myocyte contractility, confer adaptive LV remodelling. 

Retracted: No

PubPeer comments:
 u03a4his articles demonstrates a detailed description of antibodies and their use in the process of Western blotting. However, the absence of any Western blot image both in the article s body and in the article s Supplementary file renders its conclusions unsafe. The authors should explain and provide the raw data. I do not see how the declared COIs can affect the transparency and publicity of actual Western blot images.   , 
 A correction has been published: Cardiovascular Research, cvaa038, https: doi.org 10.1093 cvr cvaa038 ,