Growth factors and their roles in cardiac development and regeneration: a narrative review

Background and Objective: A network of signaling events is required for the formation of a mature cardiovascular system. During embryogenesis, secretion, or suppression of several growth factors at critical time points and proximities drive this development, including epidermal growth factors (EGFs), fibroblast growth factors (FGFs) and insulin-like growth factors (IGFs) which will be discussed in this review. Methods: PubMed was searched looking for literatures published between 1990 and March 2022 in English. A review of the literature was completed to find relevant research and terminology around the topics of cardiac development, growth factor signaling and recent advances in cardiovascular regeneration. Key Content and Findings: Each family of growth factors has been extensively examined by investigators in pre- and postnatal contexts to uncover therapeutic potential against heart disease-a leading cause of death globally. Select ligands with predicted clinical value have been further assessed, such as neuregulin-1 (NRG1)-which binds to the family of EGF receptors (EGFRs) to dimerize and ultimately activate myocyte proliferation through a signal cascade, and IGF-1-which binds to IGF receptors (IGFRs) to regulate metabolism, proliferation, apoptosis, and autophagy. Conclusions: Collectively, this review supports the need for further investigation on how these critical signaling pathways function during heart development and how the new knowledge might be leveraged to treat cardiovascular disease and promote heart regeneration.