ABSTRACT
Introduction
Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-β), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on which research has been currently focusing.
Area Covered
This review initially discusses those drugs used in clinical practice for their anti-fibrotic properties and later examines emerging pathway-specific agents in preclinical and clinical development [phase I and II-concluded or ongoing trials]. We performed a PubMed, Embase and Google Scholar research including original articles, systematic reviews, ongoing and completed trials using combinations of keywords such as ‘myocardial fibrosis’, ‘reverse remodeling’, ‘RAAs’, ‘therapy’.
Expert Opinion
A variety of preclinical evidences suggest that new drugs and molecules are potentially useful to target cardiac fibrosis and improve left ventricular function, reduce infarct size and scars, delay incident heart failure and cardiac dysfunction in animal models. However, there are very few clinical trials investigating the effect of such drugs in this setting, as well as a lack of new engineered molecules for specific targets.
Article highlights
Myocardial fibrosis represents an endogenous reparative process caused by excessive accumulation of extracellular matrix in the diseased heart.
An adaptive ‘replacement’ fibrosis must be differentiated from a maladaptive, harmful ‘reactive interstitial’ fibrosis.
Transforming Growth Factor-beta (TGF-β) is considered to be the main responsible of fibroblasts proliferation and differentiation into myofibroblasts and the main stimulus for collagen production.
TGF-β, connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on which research has been currently focusing.
None of the new antifibrotic drug therapies has currently proved to be substantially effective due to the lack in specificity.
New bioengineering techniques could pave the way for innovative cardiac target-therapies.
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose