PCSK9: Its Role in Lipid Metabolism and as a Novel Target for the Treatment of Metabolic Kidney Disease.

IF 2.1 3区医学 Q2 PERIPHERAL VASCULAR DISEASE

Current vascular pharmacology Pub Date : 2025-09-22 DOI:10.2174/0115701611392964250918094721

Hongqian Li, Ling Qi, Dongmei Zhang, Santao Ou, Weihua Wu

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引用次数: 0

Abstract

Introduction: The interplay between lipid metabolism and renal injury in the context of metabolic kidney diseases has garnered growing scientific interest. Nevertheless, the majority of existing studies have primarily concentrated on the modulation of individual lipid parameters, with relatively limited emphasis on the potential role of PCSK9 as a crucial mediator linking lipid metabolism disturbances to kidney damage.

Methods: A comprehensive literature search was performed across databases such as PubMed and Web of Science, covering the period from 2003 to 2025. Search terms included "PCSK9," "metabolic kidney disease," and "chronic kidney disease", which were used to identify relevant Randomized Controlled Trials (RCTs), systematic reviews, and mechanistic studies. In addition, proteomics data were obtained from the iProX database and integrated into the analysis.

Results: PCSK9 exacerbates lipid metabolism dysregulation through LDLR degradation. Its inhibitors improve lipid metabolism and reduce proteinuria, thereby exerting renoprotective effects via downregulation of lipid-related proteins (e.g., Angptl3) and inhibition of TGF-β signaling components.

Discussion: PCSK9 as a therapeutic target, extending prior research by demonstrating dual lipidrenal protective effects. However, evidence for rare metabolic kidney diseases and long-term safety data is lacking.

Conclusion: PCSK9 inhibitors show promise in metabolic kidney diseases, but large-scale trials are needed to clarify their long-term efficacy and optimal application scope.

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PCSK9：其在脂质代谢中的作用及作为代谢性肾病治疗的新靶点

在代谢性肾病的背景下，脂质代谢和肾损伤之间的相互作用已经引起了越来越多的科学兴趣。然而，现有的大多数研究主要集中在个体脂质参数的调节上，相对有限地强调PCSK9作为连接脂质代谢紊乱和肾损害的关键介质的潜在作用。方法：对PubMed、Web of Science等数据库进行全面的文献检索，时间跨度为2003 - 2025年。搜索词包括“PCSK9”、“代谢性肾脏疾病”和“慢性肾脏疾病”，用于识别相关的随机对照试验（RCTs）、系统评价和机制研究。此外，从iProX数据库中获得蛋白质组学数据并整合到分析中。结果：PCSK9通过LDLR降解加剧脂质代谢失调。其抑制剂通过下调脂质相关蛋白（如Angptl3）和抑制TGF-β信号成分，改善脂质代谢，减少蛋白尿，从而起到保护肾的作用。讨论：PCSK9作为治疗靶点，通过证明双脂质肾保护作用扩展了先前的研究。然而，缺乏罕见代谢性肾病的证据和长期安全性数据。结论：PCSK9抑制剂在代谢性肾脏疾病中有前景，但需要大规模试验来明确其长期疗效和最佳应用范围。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current vascular pharmacology 医学-外周血管病

CiteScore

9.20

自引率

4.40%

发文量

审稿时长

6-12 weeks

期刊介绍： Current Vascular Pharmacology publishes clinical and research-based reviews/mini-reviews, original research articles, letters, debates, drug clinical trial studies and guest edited issues to update all those concerned with the treatment of vascular disease, bridging the gap between clinical practice and ongoing research. Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials. Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units).