Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration
Top Cited Papers
Open Access
- 21 June 2016
- journal article
- review article
- Published by Springer Science and Business Media LLC in Cell and tissue research
- Vol. 365 (3), 563-581
- https://doi.org/10.1007/s00441-016-2431-9
Abstract
Ischemic cell death during a myocardial infarction leads to a multiphase reparative response in which the damaged tissue is replaced with a fibrotic scar produced by fibroblasts and myofibroblasts. This also induces geometrical, biomechanical, and biochemical changes in the uninjured ventricular wall eliciting a reactive remodeling process that includes interstitial and perivascular fibrosis. Although the initial reparative fibrosis is crucial for preventing rupture of the ventricular wall, an exaggerated fibrotic response and reactive fibrosis outside the injured area are detrimental as they lead to progressive impairment of cardiac function and eventually to heart failure. In this review, we summarize current knowledge of the mechanisms of both reparative and reactive cardiac fibrosis in response to myocardial infarction, discuss the potential of inducing cardiac regeneration through direct reprogramming of fibroblasts and myofibroblasts into cardiomyocytes, and review the currently available and potential future therapeutic strategies to inhibit cardiac fibrosis. Reparative response following a myocardial infarction. Hypoxia-induced cardiomyocyte death leads to the activation of myofibroblasts and a reparative fibrotic response in the injured area. Right top In adult mammals, the fibrotic scar formed at the infarcted area is permanent and promotes reactive fibrosis in the uninjured myocardium. Right bottom In teleost fish and newts and in embryonic and neonatal mammals, the initial formation of a fibrotic scar is followed by regeneration of the cardiac muscle tissue. Induction of post-infarction cardiac regeneration in adult mammals is currently the target of intensive research and drug discovery attemptsKeywords
Funding Information
- Terveyden Tutkimuksen Toimikunta (2666621)
- Sigrid Juséliuksen Säätiö
- Tekes (40395/13)
- Sydäntutkimussäätiö
This publication has 137 references indexed in Scilit:
- Transcription Factors MYOCD, SRF, Mesp1 and SMARCD3 Enhance the Cardio-Inducing Effect of GATA4, TBX5, and MEF2C during Direct Cellular ReprogrammingPLOS ONE, 2013
- A Thrombospondin-Dependent Pathway for a Protective ER Stress ResponseCell, 2012
- Heart repair by reprogramming non-myocytes with cardiac transcription factorsNature, 2012
- Platelet-derived growth factor involvement in myocardial remodeling following infarctionJournal of Molecular and Cellular Cardiology, 2011
- Wnt1/βcatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repairThe EMBO Journal, 2011
- Transforming growth factor (TGF)-β signaling in cardiac remodelingJournal of Molecular and Cellular Cardiology, 2011
- The origin of fibroblasts and mechanism of cardiac fibrosisJournal of Cellular Physiology, 2010
- Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined FactorsCell, 2010
- Primary contribution to zebrafish heart regeneration by gata4+ cardiomyocytesNature, 2010
- Panoramic imaging reveals basic mechanisms of induction and termination of ventricular tachycardia in rabbit heart with chronic infarction: Implications for low-voltage cardioversionHeart Rhythm, 2009