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.Graphical abstractReparative 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 attempts
Highlights
Heart failure (HF) is a major public health issue that affects more than 23 million people globally (Bui et al 2011), and because of the aging population, its prevalence is increasing
We review the potential of inducing cardiac regeneration through the direct reprogramming of fibroblasts and myofibroblasts into cardiomyocytes
The progressive reactive fibrosis elicited by biomechanical and biochemical changes in the noninfarcted myocardium after an ischemic injury plays a major role in the development of HF
Summary
Heart failure (HF) is a major public health issue that affects more than 23 million people globally (Bui et al 2011), and because of the aging population, its prevalence is increasing. The persisting activated myofibroblasts in the infarct scar continue to secrete pro-fibrotic factors that might traverse to the remote areas of the myocardium inducing activation and proliferation of local fibroblasts and increased collagen deposition in the interstitial compartment (interstitial fibrosis) and in the adventitia of coronary vessels (perivascular fibrosis; Weber et al 2013). It is expressed and activated by fibroblasts, myofibroblasts, and macrophages in the heart, and by acting on its type I receptor (AT1 receptor), it up-regulates the expression of TGF-β and IL-6 in cardiomyocytes, fibroblasts, and myofibroblasts Both Ang II and TGF-β synthesized and secreted at the infarction site have been suggested to play a role in the development of reactive fibrosis in the noninfarcted myocardium (Weber et al 2013). Statins and other cardiovascular drugs currently in use are, not efficient enough in blocking the progression of pathological fibrosis and remodeling, and new and more efficient anti-fibrotic drugs are needed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
