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

Fatih Arslan, Mirjam B. Smeets, Paul W. Riem Vis, Jacco C. Karper, Paul H. Quax, Lennart G. Bongartz, John H. Peters, Imo E. Hoefer, Pieter A. Doevendans, Gerard Pasterkamp, Dominique P. De Kleijn

Research output: Contribution to journalArticle

98 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)582-592
Number of pages11
JournalCirculation Research
Volume108
Issue number5
DOIs
StatePublished - Mar 4 2011

Fingerprint

Fibronectins
Myocardial Infarction
Infarction
Inflammation
Leukocytes
Heart Failure
Toll-Like Receptor 2
Myofibroblasts
Extracellular Matrix Proteins
Metalloproteases
Bone Marrow Transplantation
Heart Ventricles
Extracellular Matrix
Ligation
Dilatation
Monocytes
Coronary Vessels
Myocardium
Fibrosis
Collagen

Keywords

  • heart failure
  • immune system
  • inflammation
  • myocardial infarction
  • remodeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Arslan, F., Smeets, M. B., Riem Vis, P. W., Karper, J. C., Quax, P. H., Bongartz, L. G., ... De Kleijn, D. P. (2011). Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. Circulation Research, 108(5), 582-592. https://doi.org/10.1161/CIRCRESAHA.110.224428

Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. / Arslan, Fatih; Smeets, Mirjam B.; Riem Vis, Paul W.; Karper, Jacco C.; Quax, Paul H.; Bongartz, Lennart G.; Peters, John H.; Hoefer, Imo E.; Doevendans, Pieter A.; Pasterkamp, Gerard; De Kleijn, Dominique P.

In: Circulation Research, Vol. 108, No. 5, 04.03.2011, p. 582-592.

Research output: Contribution to journalArticle

Arslan, F, Smeets, MB, Riem Vis, PW, Karper, JC, Quax, PH, Bongartz, LG, Peters, JH, Hoefer, IE, Doevendans, PA, Pasterkamp, G & De Kleijn, DP 2011, 'Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction', Circulation Research, vol. 108, no. 5, pp. 582-592. https://doi.org/10.1161/CIRCRESAHA.110.224428
Arslan, Fatih ; Smeets, Mirjam B. ; Riem Vis, Paul W. ; Karper, Jacco C. ; Quax, Paul H. ; Bongartz, Lennart G. ; Peters, John H. ; Hoefer, Imo E. ; Doevendans, Pieter A. ; Pasterkamp, Gerard ; De Kleijn, Dominique P. / Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. In: Circulation Research. 2011 ; Vol. 108, No. 5. pp. 582-592.
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AU - Quax, Paul H.

AU - Bongartz, Lennart G.

AU - Peters, John H.

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