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早餐可部分恢复2型糖尿病患者高密度脂蛋白的抗炎功能。

Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus.

作者信息

Lemmers R F H, Martens N E M A, Maas A H, van Vark-van der Zee L C, Leijten F P J, Groot-van Ruijven C M, van Hoek M, Lieverse A G, Sijbrands E J G, Haak H R, Leenen P J M, Verhoeven A J M, Dik W A, Mulder M T

机构信息

Department of Internal Medicine, Section Pharmacology and Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.

Máxima Medical Center, Internal Medicine, Eindhoven, the Netherlands.

出版信息

Atheroscler Plus. 2021 Aug 24;44:43-50. doi: 10.1016/j.athplu.2021.08.006. eCollection 2021 Oct.

Abstract

BACKGROUND AND AIMS

High-density lipoproteins (HDL) of patients with type 2 diabetes mellitus (T2DM) have impaired anti-inflammatory activities. The anti-inflammatory activity of HDL has been determined after isolation by different methods from blood mostly obtained after overnight fasting. We first determined the effect of the HDL isolation method, and subsequently the effect of food intake on the anti-inflammatory function of HDL from T2DM patients.

METHODS

Blood was collected from healthy controls and T2DM patients after an overnight fast, and from T2DM patients 3 h after breakfast ( = 17 each). HDL was isolated by a two-step density gradient ultracentrifugation in iodixanol (HDL), by sequential salt density flotation (HDL) or by PEG precipitation (HDL). The anti-inflammatory function of HDL was determined by the reduction of the TNFα-induced expression of VCAM-1 in human coronary artery endothelial cells (HCAEC) and retinal endothelial cells (REC).

RESULTS

HDL isolated by the three different methods from healthy controls inhibited TNFα-induced VCAM-1 expression in HCAEC. With apoA-I at 0.7 μM, HDL and HDL were similarly effective (16% versus 14% reduction;  = 3;  > 0.05) but less effective than HDL (28%,  < 0.05). Since ultracentrifugation removes most of the unbound plasma proteins, we used HDL for further experiments. With apoA-I at 3.2 μM, HDL from fasting healthy controls and T2DM patients reduced TNFα-induced VCAM-1 expression in HCAEC by 58 ± 13% and 51 ± 20%, respectively ( = 0.35), and in REC by 42 ± 13% and 25 ± 18%, respectively ( < 0.05). Compared to preprandial HDL, postprandial HDL from T2DM patients reduced VCAM-1 expression by 56 ± 16% (paired test:  < 0.001) in HCAEC and by 34 ± 13% (paired test:  < 0.05) in REC.

CONCLUSIONS

The anti-inflammatory activity of HDL is affected by the HDL isolation method. Two-step ultracentrifugation in an iodixanol gradient is a suitable method for HDL isolation when testing HDL anti-inflammatory function. The anti-inflammatory activity of HDL from overnight fasted T2DM patients is significantly impaired in REC but not in HCAEC. The anti-inflammatory function of HDL is partly restored by food intake.

摘要

背景与目的

2型糖尿病(T2DM)患者的高密度脂蛋白(HDL)抗炎活性受损。HDL的抗炎活性大多是在通过不同方法从隔夜禁食后采集的血液中分离出HDL后测定的。我们首先确定了HDL分离方法的影响,随后确定了食物摄入对T2DM患者HDL抗炎功能的影响。

方法

在隔夜禁食后从健康对照者和T2DM患者中采集血液,并在早餐后3小时从T2DM患者中采集血液(每组n = 17)。通过在碘克沙醇中进行两步密度梯度超速离心法(HDL)、连续盐密度浮选法(HDL)或聚乙二醇沉淀法(HDL)分离HDL。通过检测肿瘤坏死因子α(TNFα)诱导的人冠状动脉内皮细胞(HCAEC)和视网膜内皮细胞(REC)中血管细胞黏附分子-1(VCAM-1)表达的降低来确定HDL的抗炎功能。

结果

通过三种不同方法从健康对照者中分离出的HDL均抑制了TNFα诱导的HCAEC中VCAM-1的表达。当载脂蛋白A-I(apoA-I)浓度为0.7 μM时,HDL和HDL的效果相似(降低16%对14%;n = 3;P > 0.05),但不如HDL有效(降低28%,P < 0.05)。由于超速离心去除了大部分未结合的血浆蛋白,我们使用HDL进行进一步实验。当apoA-I浓度为3.2 μM时,来自空腹健康对照者和T2DM患者的HDL分别使TNFα诱导的HCAEC中VCAM-1的表达降低58 ± 13%和51 ± 20%(P = 0.35),在REC中分别降低42 ± 13%和25 ± 18%(P < 0.05)。与餐前HDL相比,T2DM患者餐后HDL使HCAEC中VCAM-1的表达降低56 ± 16%(配对检验:P < 0.001),在REC中降低34 ± 13%(配对检验:P < 0.05)。

结论

HDL的抗炎活性受HDL分离方法的影响。在检测HDL抗炎功能时,碘克沙醇梯度两步超速离心法是分离HDL的合适方法。隔夜禁食的T2DM患者的HDL在REC中的抗炎活性显著受损,但在HCAEC中未受损。食物摄入可部分恢复HDL的抗炎功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45df/9833245/d9364973060e/gr1.jpg

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