Exploring Hippo YAP/TAZ Signaling: A Novel Avenue for Cardiovascular Disorders

Significant attention has been paid to the Hippo signaling pathway and its effectors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) in cellular proliferation, survival, tissue homeostasis during development as well as cancer. While initially investigated in the context of oncogenesis, recent studies have just indicated its importance to cardiovascular diseases (CVD) like cardiac myocardial infarction (MI), cardiac hypertrophy, and heart failure (HF). This review focuses on therapeutic targets, regulatory mechanisms and signaling crosstalk between Hippo YAP/TAZ pathway with other traditional pathways like PI3K/AKT, TGF-β, WNT/β-catenin in CVD. Thus, although targeted YAP/TAZ activation in the myocardium may enhance regeneration/differentiation, its dysregulation promotes maladaptive cardiac remodeling characterized by hypertrophy and fibrosis. A better appreciation of the nuanced control on YAP/TAZ in different cardiovascular indications may point to an opportunity for precision therapeutics. In this review, we have discussed strategies to target specific components of the Hippo pathway as potential therapeutic approaches with implications for fibrosis reduction by LATS1/2 inhibition or cardiomyocyte survival promotion via MST1/2 suppression. The role of noncoding RNAs in YAP/TAZ activity modulation is further illustrated and provides us with possible therapeutic avenues that can be explored for noninvasive treatments.