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血脂异常患者中高甘油三酯血症与循环中性粒细胞亚群的关联

Associations between Hypertriglyceridemia and Circulating Neutrophil Subpopulation in Patients with Dyslipidemia.

作者信息

Genkel Vadim, Dolgushin Ilya, Baturina Irina, Savochkina Albina, Kuznetsova Alla, Pykhova Lubov, Shaposhnik Igor

机构信息

Department of Internal Medicine, Federal State Budgetary Educational Institution of Higher Education South-Ural State Medical University of the Ministry of Healthcare of the Russian Federation, Chelyabinsk 454092, Russia.

Department of Microbiology, Virology, Immunology and Laboratory Medicine, Federal State Budgetary Educational Institution of Higher Education South-Ural State Medical University of the Ministry of Healthcare of the Russian Federation, Chelyabinsk 454092, Russia.

出版信息

Int J Inflam. 2021 May 26;2021:6695468. doi: 10.1155/2021/6695468. eCollection 2021.

Abstract

BACKGROUND

There is strong evidence to suggest that the negative influence of triglyceride-rich lipoproteins (TRLs) on atherosclerosis development and progression is at least partially mediated by their proinflammatory effects. However, the effect of hypertriglyceridemia (HTG) on the subpopulation composition of circulating neutrophils has not been studied so far. The aim of this study was to examine correlations between the level of triglycerides (TGs) and the subpopulation composition of circulating neutrophils in middle-aged patients with dyslipidemia without established atherosclerotic cardiovascular diseases (ASCVDs).

METHODS

Ninety-one patients with dyslipidemia, including 22 (24.2%) patients with HTG, were enrolled in the study. Phenotying of neutrophil subpopulations was performed through flow cytometry (Navios 6/2, Beckman Coulter, USA). For phenotyping of neutrophil subpopulations, conjugated monoclonal antibodies were used: CD16, PE-Cyanine7 (Invitrogen, USA); CD11b-FITC (Beckman Coulter, USA); CD62L-PE (Beckman Coulter, USA); and CD184 (CXCR4)-PE-CF594 (BD Biosciences, USA).

RESULTS

Following the correlation analysis, the TG level directly correlated with the number of circulating leukocytes ( = 0.443; < 0.0001) and neutrophils ( = 0.311; =0.008). HTG patients displayed a significantly high number of circulating neutrophils with CD16CD11bCD62L and CD16CD11bCD62L phenotypes. TG levels directly correlated with the number of circulating neutrophils having CD16CD11bCD62L and CD16CD11bCD62L phenotypes. Following the linear regression analysis, statistically significant correlations between TG levels and neutrophil subpopulations having CD16CD11bCD62L and CD16CD11bCD62LCXCR4 phenotypes were established. Changes in TG levels could explain up to 19.1% of the variability in the number of studied neutrophil subpopulations.

CONCLUSION

Among middle-aged patients without established ASCVDs, patients with HTG demonstrated a significantly higher overall number of neutrophils and neutrophils having CD16CD11bCD62L (mature neutrophils) and CD16CD11bCD62L (immunosuppressive neutrophils) than patients with normal TG levels. The TG level was associated with an increase in the number of CD16CD11bCD62L and CD16CD11bCD62LCXCR4 (ageing neutrophils) neutrophils, adjusted for the sex and age of the patients.

摘要

背景

有充分证据表明,富含甘油三酯的脂蛋白(TRL)对动脉粥样硬化发展和进展的负面影响至少部分是由其促炎作用介导的。然而,高甘油三酯血症(HTG)对循环中性粒细胞亚群组成的影响迄今尚未得到研究。本研究的目的是检查血脂异常但未患动脉粥样硬化性心血管疾病(ASCVD)的中年患者中甘油三酯(TG)水平与循环中性粒细胞亚群组成之间的相关性。

方法

91例血脂异常患者纳入本研究,其中22例(24.2%)为HTG患者。通过流式细胞术(美国贝克曼库尔特公司的Navios 6/2)对中性粒细胞亚群进行表型分析。用于中性粒细胞亚群表型分析的是偶联单克隆抗体:CD16,藻红蛋白-花青素7(美国英杰公司);CD11b-异硫氰酸荧光素(美国贝克曼库尔特公司);CD62L-藻红蛋白(美国贝克曼库尔特公司);以及CD184(CXCR4)-藻红蛋白- CF594(美国BD生物科学公司)。

结果

相关性分析后,TG水平与循环白细胞数量直接相关(r = 0.443;P < 0.0001),与中性粒细胞数量也直接相关(r = 0.311;P = 0.008)。HTG患者循环中具有CD16⁺CD11b⁺CD62L⁻和CD16⁺CD11b⁺CD62L⁺表型的中性粒细胞数量显著增多。TG水平与具有CD16⁺CD11b⁺CD62L⁻和CD16⁺CD11b⁺CD62L⁺表型的循环中性粒细胞数量直接相关。线性回归分析后,确立了TG水平与具有CD16⁺CD11b⁺CD62L⁻和CD16⁺CD11b⁺CD62L⁺CXCR4表型的中性粒细胞亚群之间的统计学显著相关性。TG水平的变化可解释所研究中性粒细胞亚群数量变异性的19.1%。

结论

在未患ASCVD的中年患者中,HTG患者的中性粒细胞总数以及具有CD16⁺CD11b⁺CD62L⁻(成熟中性粒细胞)和CD16⁺CD11b⁺CD62L⁺(免疫抑制性中性粒细胞)表型的中性粒细胞数量显著高于TG水平正常的患者。在根据患者性别和年龄进行调整后,TG水平与具有CD16⁺CD11b⁺CD62L⁻和CD16⁺CD11b⁺CD62L⁺CXCR4(衰老中性粒细胞)表型的中性粒细胞数量增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87fe/8175187/ad127bad8f8a/IJI2021-6695468.001.jpg

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