转录共激活因子Yes相关蛋白（YAP）作为Hippo信号通路的下游效应子发挥作用，在心肌细胞存活中起着至关重要的作用。在其非磷酸化活化状态下，YAP与转录因子结合，激活下游靶基因的转录。它还通过选择性结合增强子和激活靶基因来调节细胞增殖和存活。然而,人类心力衰竭中Hippo通路的上调抑制了心脏再生并破坏了星形形成，从而防止YAP的核易位。现有文献表明，Hippo/YAP轴有助于炎症和纤维化，可能在心脏发育中发挥作用，血管和肾脏损伤。此外，它是梗死心脏肌成纤维细胞分化和纤维化的关键介质。鉴于这些见解，我们能否有针对性地利用YAP的再生潜力？在这篇综述中，我们对Hippo信号通路进行了详细讨论,并巩固了开发和干预心脏抗衰老药物的概念,以利用YAP信号作为关键靶标.
The transcriptional co-activator Yes-associated protein (YAP) functions as a downstream effector of the Hippo signaling pathway and plays a crucial role in cardiomyocyte survival. In its non-phosphorylated activated state, YAP binds to transcription factors, activating the transcription of downstream target genes. It also regulates cell proliferation and survival by selectively binding to enhancers and activating target genes. However, the upregulation of the Hippo pathway in human heart failure inhibits cardiac regeneration and disrupts astrogenesis, thus preventing the nuclear translocation of YAP. Existing literature indicates that the Hippo/YAP axis contributes to inflammation and fibrosis, potentially playing a role in the development of cardiac, vascular and renal injuries. Moreover, it is a key mediator of myofibroblast differentiation and fibrosis in the infarcted heart. Given these insights, can we harness YAP\'s regenerative potential in a targeted manner? In this
review, we provide a detailed discussion of the Hippo signaling pathway and consolidate concepts for the development and intervention of cardiac anti-aging drugs to leverage YAP signaling as a pivotal target.
