Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction

Abstract

Rationale: The extracellular matrix may induce detrimental inflammatory responses on degradation, causing adverse cardiac remodeling and heart failure. The extracellular matrix protein fibronectin-EDA-/- (EIIIA; EDA) is upregulated after tissue injury and may act as a "danger signal" for leukocytes to cause adverse cardiac remodeling after infarction. Objective: In the present study, we evaluated the role of EDA-/- in regulation of postinfarct inflammation and repair after myocardial infarction. Methods and Results: Wild-type and EDA-/- mice underwent permanent ligation of the left anterior coronary artery. Despite equal infarct size between groups (38.2±4.6% versus 38.2±2.9% of left ventricle; P=0.985), EDA -/- mice exhibited less left ventricular dilatation and enhanced systolic performance compared with wild-type mice as assessed by serial cardiac MRI measurements. In addition, EDA-/- mice exhibited reduced fibrosis of the remote area without affecting collagen production, cross-linking, and deposition in the infarct area. Subsequently, ventricular contractility and relaxation was preserved in EDA-/-. At tissue level, EDA -/- mice showed reduced inflammation, metalloproteINase 2 and 9 activity, and myofibroblast transdifferentiation. Bone marrow transplantation experiments revealed that myocardium-induced EDA-/- and not EDA-/- from circulating cells regulates postinfarct remodeling. FINally, the absence of EDA-/- reduced monocyte recruitment as well as monocytic Toll-like receptor 2 and CD49d expression after infarction. Conclusions: Our study demonstrated that parenchymal fn-EDA-/- plays a critical role in adverse cardiac remodeling after infarction. Absence of fn-EDA-/- enhances survival and cardiac performance by modulating matrix turnover and inflammation via leukocytes and fibroblasts after infarction. © 2011 American Heart Association, Inc.