Islam Rakibul, Hong Zhongkui
Department of Mechanical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
Mechanobiol Med. 2024 Dec;2(4). doi: 10.1016/j.mbm.2024.100085. Epub 2024 Aug 9.
Cardiovascular diseases (CVDs) persistently rank as a leading cause of premature death and illness worldwide. The Hippo signaling pathway, known for its highly conserved nature and integral role in regulating organ size, tissue homeostasis, and stem cell function, has been identified as a critical factor in the pathogenesis of CVDs. Recent findings underscore the significance of the Yes-associated protein (YAP) and the Transcriptional Coactivator with PDZ-binding motif (TAZ), collectively referred to as YAP/TAZ. These proteins play pivotal roles as downstream components of the Hippo pathway, in the regulation of cardiovascular development and homeostasis. YAP/TAZ can regulate various cellular processes such as cell proliferation, migration, differentiation, and apoptosis through their interactions with transcription factors, particularly those within the transcriptional enhancer associate domain (TEAD) family. The aim of this review is to provide a comprehensive overview of the current understanding of YAP/TAZ signaling in cardiovascular physiology and pathogenesis. We analyze the regulatory mechanisms of YAP/TAZ activation, explore their downstream effectors, and examine their association across numerous cardiovascular disorders, including myocardial hypertrophy, myocardial infarction, pulmonary hypertension, myocardial ischemia-reperfusion injury, atherosclerosis, angiogenesis, restenosis, and cardiac fibrosis. Furthermore, we investigate the potential therapeutic implications of targeting the YAP/TAZ pathway for the treatment of CVDs. Through this comprehensive review, our aim is to elucidate the current understanding of YAP/TAZ signaling in cardiovascular biology and underscore its potential implications for the diagnosis and therapeutic intervention of CVDs.
心血管疾病（CVDs）一直是全球过早死亡和患病的主要原因。 Hippo信号通路以其高度保守的特性以及在调节器官大小、组织稳态和干细胞功能方面的重要作用而闻名，现已被确定为心血管疾病发病机制中的一个关键因素。最近的研究结果强调了Yes相关蛋白（YAP）和具有PDZ结合基序的转录共激活因子（TAZ）的重要性，它们统称为YAP/TAZ。这些蛋白质作为Hippo通路的下游成分，在心血管发育和稳态的调节中发挥着关键作用。YAP/TAZ可以通过与转录因子，特别是转录增强子结合域（TEAD）家族中的转录因子相互作用，来调节各种细胞过程，如细胞增殖、迁移、分化和凋亡。本综述的目的是全面概述目前对YAP/TAZ信号在心血管生理和发病机制中的理解。我们分析YAP/TAZ激活的调节机制，探索其下游效应器，并研究它们在多种心血管疾病中的关联，包括心肌肥大、心肌梗死、肺动脉高压、心肌缺血-再灌注损伤、动脉粥样硬化、血管生成、再狭窄和心脏纤维化。此外，我们研究了靶向YAP/TAZ通路治疗心血管疾病的潜在治疗意义。通过这一全面综述，我们的目的是阐明目前对YAP/TAZ信号在心血管生物学中的理解，并强调其对心血管疾病诊断和治疗干预的潜在意义。
