Azhdari Manizheh, Zur Hausen Axel
Pathologie, School for Cardiovascular Diseases, Fac. Health, Medicine and Life Sciences, Maastricht university, MUMC, the Netherland.
Pharmacol Res. 2025 Jan;211:107565. doi: 10.1016/j.phrs.2024.107565. Epub 2024 Dec 25.
Wnt and Notch signaling pathways play crucial roles in the development and homeostasis of the cardiovascular system. These pathways regulate important cellular processes in cardiomyocytes, endothelial cells, and smooth muscle cells, which are the key cell types involved in the structure and function of the heart and vasculature. During embryonic development, Wnt and Notch signaling coordinate cell fate specification, proliferation, differentiation, and morphogenesis of the heart and blood vessels. In the adult cardiovascular system, these pathways continue to maintain tissue homeostasis and arrange adaptive responses to various physiological and pathological stimuli. Dysregulation of Wnt and Notch signaling has been involved in the pathogenesis of numerous cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction, and heart failure. Abnormal activation or suppression of these pathways in specific cell types can contribute to endothelial dysfunction, vascular remodeling, cardiomyocyte hypertrophy, impaired cardiac contractility and dead. Understanding the complex interplay between Wnt and Notch signaling in the cardiovascular system has led to the investigation of these pathways as potential therapeutic targets in clinical trials. In conclusion, this review summarizes the current knowledge on the roles of Wnt and Notch signaling in the development and homeostasis of cardiomyocytes, endothelial cells, and smooth muscle cells. It further discusses the dysregulation of these pathways in the context of major cardiovascular diseases and the ongoing clinical investigations targeting Wnt and Notch signaling for therapeutic intervention.
Wnt和Notch信号通路在心血管系统的发育和稳态中发挥着关键作用。这些通路调节心肌细胞、内皮细胞和平滑肌细胞中的重要细胞过程，而这些细胞类型是参与心脏和血管结构与功能的关键细胞。在胚胎发育过程中，Wnt和Notch信号协调心脏和血管的细胞命运决定、增殖、分化和形态发生。在成体心血管系统中，这些通路继续维持组织稳态，并对各种生理和病理刺激做出适应性反应。Wnt和Notch信号失调与多种心血管疾病的发病机制有关，包括动脉粥样硬化、高血压、心肌梗死和心力衰竭。这些通路在特定细胞类型中的异常激活或抑制可导致内皮功能障碍、血管重塑、心肌细胞肥大、心脏收缩力受损和死亡。了解心血管系统中Wnt和Notch信号之间的复杂相互作用，促使人们在临床试验中将这些通路作为潜在的治疗靶点进行研究。总之，本综述总结了目前关于Wnt和Notch信号在心肌细胞、内皮细胞和平滑肌细胞发育和稳态中的作用的知识。它进一步讨论了在主要心血管疾病背景下这些通路的失调，以及针对Wnt和Notch信号进行治疗干预的正在进行的临床研究。
