Lipids and Inflammation: Novel Molecular Targets and Therapeutic Implications

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current medicinal chemistry Pub Date : 2024-09-18 DOI:10.2174/0109298673311105240902053715
Laura Torlai Triglia, FILIPPO LUCA GURGOGLIONE, Federico Barocelli, Michele Bianconcini, Giampaolo Niccoli
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Abstract

Atherosclerotic cardiovascular disease represents the most common cause of death worldwide. Altered cholesterol metabolism and inflammation are major cardiovascular risk factors that underpin atherosclerotic plaque growth and destabilization. While initial evidence considered dyslipidemia and inflammation as independent atherogenic actors, growing evidence has revealed that several molecular mechanisms implicated in cholesterol metabolism participate in multiple inflammatory signalling pathways. In particular, proprotein convertase subtilisin/kexin type 9, adenosine monophosphate-activated protein kinase pathway, oxidized low-density lipoproteins, and lipoprotein (a) have been demonstrated to share concurrent atherogenic and inflammatory properties. Novel lipid-lowering therapies targeting these molecular pathways have been implemented. Mechanistic and clinical studies have addressed their hypolipidemic potential and explored their role in atherosclerosis-related vascular inflammation, and ongoing randomized clinical trials are investigating their prognostic role. The purpose of this review was to dive into the signalling pathways linking cholesterol metabolism and inflammation and outline the current evidence on the anti-inflammatory activities of the novel lipid-lowering drugs.
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脂质与炎症:新的分子靶点和治疗意义
动脉粥样硬化性心血管疾病是全球最常见的死亡原因。胆固醇代谢改变和炎症是心血管疾病的主要风险因素,是动脉粥样硬化斑块生长和不稳定的基础。虽然最初的证据认为血脂异常和炎症是独立的致动脉粥样硬化因素,但越来越多的证据表明,与胆固醇代谢有关的几种分子机制参与了多种炎症信号通路。特别是,9 型枯草酶/kexin 丙蛋白转化酶、单磷酸腺苷激活的蛋白激酶通路、氧化低密度脂蛋白和脂蛋白(a)已被证明同时具有致动脉粥样硬化和炎症的特性。针对这些分子途径的新型降脂疗法已经开始实施。机理和临床研究探讨了它们的降脂潜力,并探索了它们在动脉粥样硬化相关血管炎症中的作用,目前正在进行的随机临床试验正在研究它们的预后作用。本综述旨在深入研究连接胆固醇代谢和炎症的信号通路,并概述新型降脂药物的抗炎活性的现有证据。
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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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