Gao Jing, Pan Hongjie, Guo Xiaogang, Huang Yu, Luo Jiang-Yun
Department of Cardiology, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, China.
Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, China.
Cell Signal. 2025 Jun;130:111699. doi: 10.1016/j.cellsig.2025.111699. Epub 2025 Feb 27.
This review presents an overview of the regulation, function, disease-relevance and pharmacological regulation of the critical endothelial transcription factors KLF2/4 in vasculature. The regulatory mechanisms of KLF2/4 expression and activity in vascular endothelium in response to hemodynamic forces and biochemical stimuli are depicted. The functional effects mediated by direct or indirect target genes of KLF2/4 in endothelial cells are systematically summarized. The contributory roles that dysregulated KLF2/4 play in relevant cardiovascular pathologies, such as atherosclerotic vascular lesions, pulmonary arterial hypertension and vascular complications of diabetes were reviewed. Moreover, this review also discusses the pharmacological regulation of KLF2/4 by drugs used in clinics and therapeutic possibility by directly targeting these two transcription factors for treating atherosclerotic cardiovascular diseases. Finally, prospective opinions on the gaps in disclosing novel vascular function mediated by KLF2/4 and future research needs are expressed.
本综述概述了关键内皮转录因子KLF2/4在脉管系统中的调控、功能、与疾病的相关性及药理学调控。描述了血管内皮中KLF2/4表达和活性响应血流动力学力和生化刺激的调控机制。系统总结了KLF2/4在内皮细胞中直接或间接靶基因介导的功能效应。综述了KLF2/4失调在相关心血管疾病（如动脉粥样硬化性血管病变、肺动脉高压和糖尿病血管并发症）中所起的作用。此外，本综述还讨论了临床使用药物对KLF2/4的药理学调控以及直接靶向这两种转录因子治疗动脉粥样硬化性心血管疾病的治疗可能性。最后，对揭示KLF2/4介导的新型血管功能方面的差距及未来研究需求表达了前瞻性观点。
