The effects of YAP/TAZ in cardiomyocytes: a scoping review

Abstract

The Hippo signaling pathway, through its effectors' yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), plays a pivotal role in heart development, regeneration, and repair. Despite the well-recognized role of YAP in promoting cardiomyocyte proliferation and differentiation, the underlying mechanisms require further explanation. Therefore, this scoping review was conducted to explore the underlying mechanisms of YAP and TAZ in cardiomyocyte biology. In this scoping review, 138 studies were screened using PRISMA extension for scoping reviews guidelines to examine the upstream regulators, mechanisms, and therapeutic potential of YAP/TAZ in cardiomyocytes. Articles were selected based on relevance to YAP/TAZ signaling in cardiac regeneration and focused on upstream regulators, signaling pathways, and therapeutic applications. Data were extracted using standardized forms, and thematic analysis was performed iteratively. YAP activation regulated several processes, including cardiomyocyte proliferation, differentiation, and protection against oxidative stress. Mechanotransduction factors influence YAP activity, linking the biomechanical environment to cardiac regeneration. Novel upstream regulators, such as prorenin receptors, melatonin, and ERBB2, were identified as YAP/TAZ modulators. Moreover, downstream pathways such as Wnt/β-catenin, PI3K/Akt, and TLR-mediated inflammation confer their effects on cellular proliferation, mitochondrial dynamics, and inflammation. Several therapeutic targets involving YAP that could enhance cardiac regeneration while reducing fibrosis and inflammation were identified. However, significant research gaps remain, including the underexplored role of TAZ, necessity for in vivo studies and transcriptomics to elucidate cell-specific effects, and intricate regulatory networks of YAP/TAZ.

Keywords: Cardiomyocytes; Myocardial injury; Myocardial regeneration; Transcriptional coactivator with PDZ-binding motif; Yes-associated protein.