Figure 3. Promising therapeutic targets to mediate CF activation and fibrosis.

Based on recent studies, there are several avenues that can be further explored for their potential to alleviate cardiac fibrosis. It is likely that a combination of these approaches will efficiently combat the progression of fibrosis after injury or disease. 1) The extracellular matrix (ECM) can be targeted with inhibitors of crosslinking and fibrillogenesis, or indirectly through changing cell-derived expression of ECM factors. 2) Cell surface receptors and downstream signaling cascades can be used for targeted pathway inhibition, including signaling cascades like transforming growth factor-beta, p38/MAPK (mitogen-activated protein kinase) and Yap/Taz. 3) Cell surface markers can be used to identify and target unwanted cells, such as FAP recognition of CAR (chimeric antigen receptor) T cells. This approach may also be utilized to target macrophage subpopulations. 4) Post-transcriptional modifiers, such as muscleblind-like 1 (MBNL1) and histone deacetylases (HDACs), could be exploited to alter RNA transcript stability and subsequent cell activation. 5) Cell activation may be modified by regulating epigenetic modifications and transcription factor expression (HMGA1, high-mobility group A1).