Cardiac fibrosis is a prevalent pathological feature in the progression of various cardiovascular diseases, including heart failure, myocardial infarction, and dilated cardiomyopathy, particularly in their advanced stages. Its primary mechanism involves the abnormal activation of cardiac fibroblasts and excessive deposition of extracellular matrix, which ultimately results in decreased myocardial compliance and cardiac dysfunction. The Hippo signaling pathway, an evolutionary conserved kinase cascade, not only regulates organ development and tissue homeostasis but has also been shown to play a critical role in cardiac fibrosis. Notably, the Hippo pathway demonstrates cell-specific regulatory functions across different cardiac cell types, including cardiomyocytes, fibroblasts, and immune cells. This systematic review elucidates the molecular mechanisms by which the Hippo pathway influences cardiac fibrosis, emphasizing its cell type-dependent roles. It analyzes the complexity of its roles from the perspectives of cross-talk between pathways, various types of cardiac diseases, and different stages of disease progression. Additionally, it summarizes recent advancements in anti-fibrotic drugs that target this pathway, thereby providing a theoretical foundation for the development of novel therapeutic strategies in cardiac fibrosis.
Qiu et al. (Tue,) studied this question.