动脉粥样硬化中的脂肪连接素和脂肪连接素受体

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine reviews Pub Date : 2024-08-06 DOI:10.1210/endrev/bnae021
Ioanna Gianopoulos, Christos S Mantzoros, Stella S Daskalopoulou
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引用次数: 0

摘要

脂肪连通素是一种大量分泌的激素,可在脂肪组织、免疫系统和心血管系统之间传递信息。在新陈代谢健康的人体内,脂肪连通素的含量通常很高,有助于改善外周组织对胰岛素的反应、葡萄糖耐量和脂肪酸氧化。除了在胰岛素敏感组织中发挥新陈代谢功能外,脂肪连通素还部分通过调节巨噬细胞介导的反应,在减少动脉粥样硬化斑块的形成方面发挥着重要作用。在这种情况下,脂肪连通素与其受体--巨噬细胞细胞表面的脂肪连通素受体 1(AdipoR1)和 AdipoR2 结合,激活下游信号级联,诱导特定的动脉粥样硬化保护功能。值得注意的是,巨噬细胞通过在促炎症反应介质和抗炎症促溶解介质之间切换的能力来调节斑块的稳定性。传统上,巨噬细胞极化谱的两极包括 M1 促炎表型和 M2 抗炎表型。以往的证据表明,脂肪连通素-AdipoR通路影响着M1-M2巨噬细胞的极化;脂肪连通素促进向类似M2的状态转变,而AdipoR1-和AdipoR2-特异性的贡献则更为细微。为了深入探讨这些概念,我们在这篇综述中讨论了脂肪连接素和 AdipoR1/R2 对 1)代谢和免疫反应以及 2)M1-M2 巨噬细胞极化的影响,包括它们减轻动脉粥样硬化斑块炎症的能力,以及它们作为临床应用治疗靶点的潜力。
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Adiponectin and Adiponectin Receptors in Atherosclerosis.

Adiponectin is an abundantly secreted hormone that communicates information between the adipose tissue, and the immune and cardiovascular systems. In metabolically healthy individuals, adiponectin is usually found at high levels and helps improve insulin responsiveness of peripheral tissues, glucose tolerance, and fatty acid oxidation. Beyond its metabolic functions in insulin-sensitive tissues, adiponectin plays a prominent role in attenuating the development of atherosclerotic plaques, partially through regulating macrophage-mediated responses. In this context, adiponectin binds to its receptors, adiponectin receptor 1 (AdipoR1) and AdipoR2 on the cell surface of macrophages to activate a downstream signaling cascade and induce specific atheroprotective functions. Notably, macrophages modulate the stability of the plaque through their ability to switch between pro-inflammatory responders, and anti-inflammatory pro-resolving mediators. Traditionally, the extremes of the macrophage polarization spectrum span from M1 pro-inflammatory and M2 anti-inflammatory phenotypes. Previous evidence has demonstrated that the adiponectin-AdipoR pathway influences M1-M2 macrophage polarization; adiponectin promotes a shift towards an M2-like state, whereas AdipoR1- and AdipoR2-specific contributions are more nuanced. To explore these concepts in depth, we discuss in this review the impact of adiponectin and AdipoR1/R2 on 1) metabolic and immune responses, and 2) M1-M2 macrophage polarization, including their ability to attenuate atherosclerotic plaque inflammation, and their potential as therapeutic targets for clinical applications.

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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
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