Melusin protects from cardiac rupture and improves functional remodelling after myocardial infarction

Bernhard Unsoeld, Axel Kaul, Mauro Sbroggi, Carola Schubert, Vera Regitz-Zagrosek, Mara Brancaccio, Federico Damilano, Emilio Hirsch, Marc Van Bilsen, Chantal Munts, Karin Sipido, Virginie Bito, Elke Detre, Nana Maria Wagner, Katrin Schaefer, Tim Seidler, Johannes Vogt, Stefan Neef, Annalen Bleckmann, Lars S. MaierJean Luc Balligand, Caroline Bouzin, Renee Ventura-Clapier, Anne Garnier, Thomas Eschenhagen, Ali El-Armouche, Ralph Knoell, Guido Tarone*, Gerd Hasenfuss

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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. 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 melusins 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. 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.
Original languageEnglish
Pages (from-to)97-107
JournalCardiovascular Research
Issue number1
Publication statusPublished - 1 Jan 2014


  • Infarction
  • Chaperon
  • Map kinase
  • Remodelling
  • Transgenic animal models

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