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颗粒蛋白前体在心血管疾病中的保护机制及治疗潜力

Progranulin's Protective Mechanisms and Therapeutic Potential in Cardiovascular Disease.

作者信息

Qiao Gan, Lu Yongxiang, Wu Jianping, Ren Chunyang, Lin Roudian, Zhang Chunxiang

机构信息

Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.

Nucleic Acid Medicine of Luzhou Key Laboratory, Central Nervous System Drug Key Laboratory of Sichuan Province, Southwest Medical University, Luzhou 646000, China.

出版信息

Cells. 2025 May 22;14(11):762. doi: 10.3390/cells14110762.

Abstract

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality globally, prompting the investigation of novel therapeutic targets. Progranulin (PGRN), a glycoprotein initially associated with neurodegenerative disorders, has emerged as a critical protective agent in cardiovascular health. Recent studies indicate that PGRN exerts its protective effects through various mechanisms, including the modulation of inflammatory pathways, enhancement of mitochondrial function, and promotion of vascular integrity. By engaging with key signaling pathways, such as PI3K/Akt, NF-κB and Wnt/β-catenin, PGRN mitigates oxidative stress and fosters an environment conducive to cardiac repair following ischemic injury. Furthermore, PGRN's role in lipid metabolism and vascular smooth muscle cell behavior highlights its complexity in influencing atherogenesis and vascular homeostasis. This review synthesizes current knowledge regarding PGRN's protective mechanisms in CVD, emphasizing its potential as a therapeutic target and paving the way for innovative approaches to prevent and treat cardiovascular diseases, ultimately improving patient outcomes in this critical area of public health.

摘要

心血管疾病(CVD)仍然是全球发病和死亡的主要原因,这促使人们对新的治疗靶点进行研究。颗粒蛋白前体(PGRN)是一种最初与神经退行性疾病相关的糖蛋白,已成为心血管健康中的关键保护因子。最近的研究表明,PGRN通过多种机制发挥其保护作用,包括调节炎症途径、增强线粒体功能以及促进血管完整性。通过参与关键信号通路,如PI3K/Akt、NF-κB和Wnt/β-连环蛋白,PGRN减轻氧化应激,并在缺血性损伤后营造有利于心脏修复的环境。此外,PGRN在脂质代谢和血管平滑肌细胞行为中的作用凸显了其在影响动脉粥样硬化和血管稳态方面的复杂性。本综述综合了目前关于PGRN在CVD中保护机制的知识,强调了其作为治疗靶点的潜力,并为预防和治疗心血管疾病的创新方法铺平道路,最终改善这一关键公共卫生领域的患者预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64a4/12153738/8d445a1668ae/cells-14-00762-g001.jpg

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