HSPB1调节炎症反应在动脉粥样硬化作用机制及靶向治疗的研究进展

Advances in HSPB1-mediated inflammatory regulation and targeted therapeutic strategies in atherosclerosis

摘要:

动脉粥样硬化(As)是一种慢性炎症性疾病,持续存在的炎症反应是驱动斑块形成与发展的重要机制。热休克蛋白家族B成员1(HSPB1)属于小分子热休克蛋白家族,作为一种分子伴侣,在多种细胞和组织中广泛表达。HSPB1的表达受热休克转录因子1(HSF1)调控,HSF1通过与热休克元件(HSE)结合直接激活其转录。近年来研究表明,HSPB1在As进程中发挥重要作用,主要通过调控炎症因子表达、影响脂质代谢及调控细胞程序性死亡等途径,抑制斑块炎症反应,从而发挥抗As的作用。本综述系统阐述了HSPB1通过多种方式抑制炎症反应以调控As进展的机制,并进一步梳理了靶向干预HSPB1的抗As治疗策略,包括特异性激动剂的开发以及纳米药物递送系统(NDDS)的创新应用,以期为As的预防和治疗提供新的理论依据和治疗方向。

Abstract:

Atherosclerosis (As) is a chronic inflammatory disease, in which persistent inflammation serves as a key mechanism driving plaque formation and progression. Heat shock protein family B member 1 (HSPB1), a member of the small heat shock protein family, functions as a molecular chaperone and is widely expressed in various cells and tissues. The expression of HSPB1 is regulated by heat shock factor 1 (HSF1), which directly activates its transcription by binding to the heat shock element (HSE). Recent studies have revealed that HSPB1 plays an important role in the progression of atherosclerosis, primarily by modulating the expression of inflammatory factors, influencing lipid metabolism, and regulating programmed cell death, thereby attenuating plaque inflammation and exerting anti-atherosclerotic effects. This review systematically elaborates on the mechanisms by which HSPB1 suppresses inflammatory responses to modulate the progression of As, and further summarizes HSPB1-targeted therapeutic strategies for atherosclerosis, including the development of specific agonists and innovative applications of nano-drug delivery system (NDDS), aiming to provide new theoretical foundations and therapeutic directions for the prevention and treatment of As.