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血管炎症中的Krüppel样因子:机制洞察与治疗潜力

Krüppel-Like Factors in Vascular Inflammation: Mechanistic Insights and Therapeutic Potential.

作者信息

Sweet David R, Fan Liyan, Hsieh Paishiun N, Jain Mukesh K

机构信息

Case Cardiovascular Research Institute, Case Western Reserve University, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States.

Department of Pathology, Case Western Reserve University, Cleveland, OH, United States.

出版信息

Front Cardiovasc Med. 2018 Feb 5;5:6. doi: 10.3389/fcvm.2018.00006. eCollection 2018.

Abstract

The role of inflammation in vascular disease is well recognized, involving dysregulation of both circulating immune cells as well as the cells of the vessel wall itself. Unrestrained vascular inflammation leads to pathological remodeling that eventually contributes to atherothrombotic disease and its associated sequelae (e.g., myocardial/cerebral infarction, embolism, and critical limb ischemia). Signaling events during vascular inflammation orchestrate widespread transcriptional programs that affect the functions of vascular and circulating inflammatory cells. The Krüppel-like factors (KLFs) are a family of transcription factors central in regulating vascular biology in states of homeostasis and disease. Given their abundance and diversity of function in cells associated with vascular inflammation, understanding the transcriptional networks regulated by KLFs will further our understanding of the pathogenesis underlying several pervasive health concerns (e.g., atherosclerosis, stroke, etc.) and consequently inform the treatment of cardiovascular disease. Within this review, we will discuss the role of KLFs in coordinating protective and deleterious responses during vascular inflammation, while addressing the potential targeting of these critical transcription factors in future therapies.

摘要

炎症在血管疾病中的作用已得到充分认识,涉及循环免疫细胞以及血管壁自身细胞的失调。不受控制的血管炎症会导致病理重塑,最终促成动脉粥样硬化血栓形成疾病及其相关后遗症(如心肌/脑梗死、栓塞和严重肢体缺血)。血管炎症期间的信号事件精心编排了广泛的转录程序,这些程序会影响血管和循环炎症细胞的功能。Krüppel样因子(KLFs)是一类转录因子,在稳态和疾病状态下调节血管生物学过程中起着核心作用。鉴于它们在与血管炎症相关的细胞中的丰富性和功能多样性,了解由KLFs调控的转录网络将有助于我们进一步理解几种普遍存在的健康问题(如动脉粥样硬化、中风等)的发病机制,从而为心血管疾病的治疗提供依据。在本综述中,我们将讨论KLFs在协调血管炎症期间的保护性和有害性反应中的作用,同时探讨在未来治疗中对这些关键转录因子进行靶向治疗的可能性。

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