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脂质与炎症:新型分子靶点及治疗意义

Lipids and Inflammation: Novel Molecular Targets and Therapeutic Implications.

作者信息

Triglia Laura Torlai, Gurgoglione Filippo Luca, Barocelli Federico, Bianconcini Michele, Niccoli Giampaolo

机构信息

Division of Cardiology, University of Parma, Parma University Hospital, Parma, Italy.

Division of Cardiology, Parma University Hospital, Parma, Italy.

出版信息

Curr Med Chem. 2024 Sep 16. doi: 10.2174/0109298673311105240902053715.

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.

摘要

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动脉粥样硬化斑块生长和不稳定的主要心血管危险因素。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,参与胆固醇代谢的几种分子机制也参与了多种炎症信号通路。特别是,前蛋白转化酶枯草杆菌蛋白酶/kexin 9型、腺苷单磷酸激活蛋白激酶途径、氧化型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特性。针对这些分子途径的新型降脂疗法已经实施。机制研究和临床研究探讨了它们的降血脂潜力,并探索了它们在动脉粥样硬化相关血管炎症中的作用,正在进行的随机临床试验正在研究它们的预后作用。这篇综述的目的是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抗炎活性的现有证据。

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