[Treatment of cardiac fibrosis: from neurohormonal antagonists to CAR-T cells]

: Cardiac fibrosis is characterized by the deposition of extracellular matrix proteins in the spaces between cardiomyocytes following both acute and chronic tissue damage events, resulting in the remodeling and stiffening of heart tissue. Fibrosis plays an important role in the pathogenesis of many cardiovascular disorders, including heart failure and myocardial infarction. Several studies have identified fibroblasts, which are induced to differentiate into myofibroblasts in response to various types of damage, as one of the most important cell types involved in the fibrotic process. There are currently no drugs with primarily antifibrotic action approved for clinical use, as the evidence of a clinical efficacy of these drugs is extremely limited, despite the numerous encouraging results from experimental studies. A new approach is represented by the use of chimeric antigen receptor T cells engineered in vivo using lipid nanoparticles containing mRNA encoding a receptor directed against the fibroblast activation protein, expressed by activated cardiac fibroblasts. This strategy has proved to be safe and effective in reducing myocardial fibrosis and improving cardiac function in mouse models of cardiac fibrosis. Clinical studies are required to test this novel approach in humans.