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脂联素的血管效应:分子机制与潜在治疗干预

Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention.

作者信息

Zhu Weidong, Cheng Kenneth K Y, Vanhoutte Paul M, Lam Karen S L, Xu Aimin

机构信息

Department of Medicine, University of Hong Kong, Hong Kong, People's Republic of China.

出版信息

Clin Sci (Lond). 2008 Mar;114(5):361-74. doi: 10.1042/CS20070347.

Abstract

Adiponectin is a major adipocyte-secreted adipokine abundantly present in the circulation as three distinct oligomeric complexes. In addition to its role as an insulin sensitizer, mounting evidence suggests that adiponectin is an important player in maintaining vascular homoeostasis. Numerous epidemiological studies based on different ethnic groups have identified adiponectin deficiency (hypoadiponectinaemia) as an independent risk factor for endothelial dysfunction, hypertension, coronary heart disease, myocardial infarction and other cardiovascular complications. Conversely, elevation of circulating adiponectin concentrations by either genetic or pharmacological approaches can alleviate various vascular dysfunctions in animal models. Adiponectin exerts its vasculoprotective effects through its direct actions in the vascular system, such as increasing endothelial NO production, inhibiting endothelial cell activation and endothelium-leucocyte interaction, enhancing phagocytosis, and suppressing macrophage activation, macrophage-to-foam cell transformation and platelet aggregation. In addition, adiponectin reduces neointima formation through an oligomerization-dependent inhibition of smooth muscle proliferation. The present review highlights recent research advances in unveiling the molecular mechanisms that underpin the vascular actions of adiponectin and discusses the potential strategies of using adiponectin or its signalling pathways as therapeutic targets to combat obesity-related metabolic and vascular diseases.

摘要

脂联素是一种主要由脂肪细胞分泌的脂肪因子,以三种不同的寡聚体复合物形式大量存在于循环系统中。除了作为胰岛素增敏剂的作用外,越来越多的证据表明脂联素在维持血管稳态中起着重要作用。基于不同种族群体的大量流行病学研究已将脂联素缺乏(低脂联素血症)确定为内皮功能障碍、高血压、冠心病、心肌梗死和其他心血管并发症的独立危险因素。相反,通过基因或药理学方法提高循环脂联素浓度可缓解动物模型中的各种血管功能障碍。脂联素通过其在血管系统中的直接作用发挥血管保护作用,例如增加内皮一氧化氮生成、抑制内皮细胞活化和内皮-白细胞相互作用、增强吞噬作用以及抑制巨噬细胞活化、巨噬细胞向泡沫细胞转化和血小板聚集。此外,脂联素通过依赖寡聚化抑制平滑肌增殖来减少新生内膜形成。本综述重点介绍了揭示脂联素血管作用分子机制的最新研究进展,并讨论了将脂联素或其信号通路用作治疗靶点以对抗肥胖相关代谢和血管疾病的潜在策略。

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