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

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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Unsöld B,Kaul A,Sbroggiò M,Schubert C,Regitz-Zagrosek V,Brancaccio M,Damilano F,Hirsch E,Van Bilsen M,Munts C,Sipido K,Bito V,Detre E,Wagner NM,Schäfer K,Seidler T,Vogt J,Neef S,Bleckmann A,Maier LS,Balligand JL,

doi

10.1093/cvr/cvt235

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

97-107

issue

eissn

0008-6363

issn

1755-3245

pii

cvt235

journal_volume

101

pub_type

杂志文章,多中心研究

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