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外周血单核细胞提取 VEGF 蛋白水平和 VEGF mRNA:与健康人群中炎症分子的关系。

Peripheral blood mononuclear cells extracts VEGF protein levels and VEGF mRNA: Associations with inflammatory molecules in a healthy population.

机构信息

Université de Lorraine, Inserm, IGE-PCV, Nancy, France.

Randox Laboratories Limited, Crumlin, Co. Antrim, Northern Ireland, United Kingdom.

出版信息

PLoS One. 2019 Aug 16;14(8):e0220902. doi: 10.1371/journal.pone.0220902. eCollection 2019.

Abstract

BACKGROUND

Vascular endothelial growth factor (VEGF) is a signal protein, implicated in various physiological and pathophysiological processes together with other common inflammatory biomarkers. However, their associations have not yet been fully elucidated. In the present study, we investigated associations between VEGF and four specific VEGF mRNA isoforms with levels of 11 inflammation molecules, derived from peripheral blood mononuclear cells (PBMCs) extracts.

METHODS

Healthy participants from the STANISLAS Family Study (n = 285) were included. Levels of VEGF (four mRNA isoforms and protein levels) and inflammatory molecules (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, INF-γ, TNF-α, MCP-1, EGF) were measured in PBMCs extracts. Multiple regression analyses were performed, adjusted for age and gender.

RESULTS

The analyses revealed significant associations between VEGF protein levels and levels of IL-4 (β = 0.028, P = 0.013), MCP-1 (β = 0.015, P<0.0001) and EGF (β = 0.017, P<0.0001). Furthermore, mRNA isoform VEGF165 was associated with MCP-1 and IL-1α (P = 0.002 and P = 0.008, respectively); and mRNA isoform VEGF189 was associated with IL-4 and IL-6 (P = 0.019 and P = 0.034, respectively).

CONCLUSIONS

To our knowledge, the present study represents the first investigation that successfully demonstrates links between VEGF protein levels and inflammatory molecules levels derived from PBMCs extracts and identifies associations between specific VEGF mRNA isoforms and inflammatory molecules.

IMPACT

These findings provide novel insights that may assist in the development of new tissue and mRNA isoform specific measurements of VEGF levels, which may positively contribute to predicting the risk of common complex diseases and response of currently used anti-VEGF agents, and developing of novel targeted therapies for VEGF-related pathophysiology.

摘要

背景

血管内皮生长因子 (VEGF) 是一种信号蛋白,与其他常见炎症生物标志物一起参与各种生理和病理生理过程。然而,它们的关联尚未完全阐明。在本研究中,我们研究了 VEGF 与外周血单核细胞 (PBMC) 提取物中 11 种炎症分子的四种特定 VEGF mRNA 亚型之间的关联。

方法

本研究纳入了 STANISLAS 家族研究(n=285)的健康参与者。测量了 PBMC 提取物中 VEGF(四种 mRNA 亚型和蛋白水平)和炎症分子(IL-1α、IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10、INF-γ、TNF-α、MCP-1、EGF)的水平。进行了多元回归分析,调整了年龄和性别。

结果

分析显示 VEGF 蛋白水平与 IL-4(β=0.028,P=0.013)、MCP-1(β=0.015,P<0.0001)和 EGF(β=0.017,P<0.0001)水平之间存在显著关联。此外,VEGF165 mRNA 亚型与 MCP-1 和 IL-1α 相关(P=0.002 和 P=0.008);VEGF189 mRNA 亚型与 IL-4 和 IL-6 相关(P=0.019 和 P=0.034)。

结论

据我们所知,本研究首次成功地证明了 PBMCs 提取物中 VEGF 蛋白水平与炎症分子水平之间的联系,并确定了特定 VEGF mRNA 亚型与炎症分子之间的关联。

影响

这些发现提供了新的见解,可能有助于开发新的组织和特定于 mRNA 亚型的 VEGF 水平测量方法,这可能有助于预测常见复杂疾病的风险和目前使用的抗 VEGF 药物的反应,并为 VEGF 相关病理生理学开发新的靶向治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ff3/6697334/22d50d2fd404/pone.0220902.g001.jpg

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