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载脂蛋白C-III循环水平与炎症生物标志物之间的非甘油三酯依赖性关联。

Triglyceride-independent associations between circulating levels of apolipoprotein C-III and biomarkers of inflammation.

作者信息

Llop Dídac, Rehues Pere, Paredes Silvia, Guardiola Montse, Girona Josefa, Rosales Roser, Esteban Yaiza, Masana Lluís, Ibarretxe Daiana, Vallvé Joan-Carles, Ribalta Josep

机构信息

Facultat de Medicina i Ciències de la Salut, Unitat de Recerca en Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Reus, Spain.

Institut d'Investigació Sanitària Pere Virgili, Reus, Spain.

出版信息

Cardiovasc Diabetol. 2025 Jan 8;24(1):9. doi: 10.1186/s12933-024-02553-z.

DOI:10.1186/s12933-024-02553-z
PMID:39780204
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11715487/
Abstract

BACKGROUNDS AND AIMS

Preclinical studies suggest that a triglyceride (TG)-independent proinflammatory action of apolipoprotein C-III (apoCIII) exists. We aimed to investigate the relationship between circulating apoCIII levels and subclinical inflammation markers across different cohorts with distinctive inflammatory patterns: patients with metabolic disorders (MDs), patients with rheumatoid arthritis (RA), and controls. Specifically, we assessed the associations of apoCIII with acute inflammation biomarkers (e.g., high sensitivity C-reactive protein (hsCRP)) and novel systemic inflammation biomarkers (e.g., glycosylated proteins: Glyc-A, Glyc-B, Glyc-F), aiming to understand the role of apoCIII beyond its traditional function in TG metabolism.

METHODS

This cross-sectional study involved 1242 participants: 906 patients with MD (metabolic syndrome, type 2 diabetes (T2DM) and/or obesity), 192 patients with RA, and 144 controls. ApoCIII and hsCRP levels were measured via immunoturbidimetric assays, and glycosylated proteins were quantified via 1 H-NMR spectroscopy. Correlation and multivariate linear regression analyses were conducted.

RESULTS

ApoCIII levels were significantly and positively associated with Glyc-A, Glyc-B, and Glyc-F levels across all cohorts. Most of these associations remained significant in the MD group after adjusting for TG levels. Conversely, negative associations were detected between apoCIII and hsCRP patients with MD and RA, which were maintained after including TG in the models.

CONCLUSION

In patients with MD and RA, circulating apoCIII levels were positively associated with glycoproteins and negatively with hsCRP, in a TG-independent manner. Our results suggest that apoCIII is associated with the low-grade inflammatory profile represented by glycoproteins, independent of triglyceride levels. Additionally, we observed a negative association with hsCRP, which, while seemingly paradoxical, has been reported in previous studies.

摘要

背景与目的

临床前研究表明,载脂蛋白C-III(apoCIII)存在不依赖甘油三酯(TG)的促炎作用。我们旨在研究不同炎症模式队列中循环apoCIII水平与亚临床炎症标志物之间的关系,这些队列包括:代谢紊乱(MD)患者、类风湿关节炎(RA)患者和对照组。具体而言,我们评估了apoCIII与急性炎症生物标志物(如高敏C反应蛋白(hsCRP))和新型全身炎症生物标志物(如糖基化蛋白:Glyc-A、Glyc-B、Glyc-F)之间的关联,旨在了解apoCIII在TG代谢中传统功能之外的作用。

方法

这项横断面研究纳入了1242名参与者:906名MD患者(代谢综合征、2型糖尿病(T2DM)和/或肥胖)、192名RA患者和144名对照组。通过免疫比浊法测量apoCIII和hsCRP水平,通过1H-NMR光谱法定量糖基化蛋白。进行了相关性和多元线性回归分析。

结果

在所有队列中,apoCIII水平与Glyc-A、Glyc-B和Glyc-F水平均呈显著正相关。在调整TG水平后,MD组中的大多数这些关联仍然显著。相反,在MD和RA患者中检测到apoCIII与hsCRP之间存在负相关,在模型中纳入TG后这种负相关仍然存在。

结论

在MD和RA患者中,循环apoCIII水平与糖蛋白呈正相关,与hsCRP呈负相关且不依赖于TG。我们的结果表明,apoCIII与糖蛋白所代表的低度炎症特征相关,独立于甘油三酯水平。此外,我们观察到与hsCRP存在负相关,虽然这看似矛盾,但先前的研究中已有报道。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab3d/11715487/bda8d35c7ef3/12933_2024_2553_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab3d/11715487/2fe7b130d0da/12933_2024_2553_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab3d/11715487/9876540c5679/12933_2024_2553_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab3d/11715487/08297212b48e/12933_2024_2553_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab3d/11715487/bda8d35c7ef3/12933_2024_2553_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab3d/11715487/2fe7b130d0da/12933_2024_2553_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab3d/11715487/9876540c5679/12933_2024_2553_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab3d/11715487/08297212b48e/12933_2024_2553_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab3d/11715487/bda8d35c7ef3/12933_2024_2553_Fig4_HTML.jpg

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Int J Mol Sci. 2024 Nov 27;25(23):12759. doi: 10.3390/ijms252312759.
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Cardiovasc Diabetol. 2024 Dec 4;23(1):433. doi: 10.1186/s12933-024-02531-5.
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Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk.
Olezarsen 治疗心血管疾病高危患者的高三酰甘油血症。
N Engl J Med. 2024 May 16;390(19):1770-1780. doi: 10.1056/NEJMoa2402309. Epub 2024 Apr 7.
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Apolipoprotein C3 induces inflammasome activation only in its delipidated form.载脂蛋白 C3 只有在去脂形式下才能诱导炎症小体激活。
Nat Immunol. 2023 Mar;24(3):408-411. doi: 10.1038/s41590-023-01423-2. Epub 2023 Feb 13.
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