PMID- 36644668 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230117 IS - 2667-0895 (Electronic) IS - 2667-0909 (Print) IS - 2667-0895 (Linking) VI - 44 DP - 2021 Oct TI - Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus. PG - 43-50 LID - 10.1016/j.athplu.2021.08.006 [doi] AB - 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 ex vivo 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 (n = 17 each). HDL was isolated by a two-step density gradient ultracentrifugation in iodixanol (HDL(DGUC2)), by sequential salt density flotation (HDL(SEQ)) or by PEG precipitation (HDL(PEG)). The anti-inflammatory function of HDL was determined by the reduction of the TNFalpha-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 TNFalpha-induced VCAM-1 expression in HCAEC. With apoA-I at 0.7 muM, HDL(DGUC2) and HDL(SEQ) were similarly effective (16% versus 14% reduction; n = 3; p > 0.05) but less effective than HDL(PEG) (28%, p < 0.05). Since ultracentrifugation removes most of the unbound plasma proteins, we used HDL(DGUC2) for further experiments. With apoA-I at 3.2 muM, HDL from fasting healthy controls and T2DM patients reduced TNFalpha-induced VCAM-1 expression in HCAEC by 58 +/- 13% and 51 +/- 20%, respectively (p = 0.35), and in REC by 42 +/- 13% and 25 +/- 18%, respectively (p < 0.05). Compared to preprandial HDL, postprandial HDL from T2DM patients reduced VCAM-1 expression by 56 +/- 16% (paired test: p < 0.001) in HCAEC and by 34 +/- 13% (paired test: p < 0.05) in REC. CONCLUSIONS: The ex vivo 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. CI - (c) 2021 The Authors. FAU - Lemmers, R F H AU - Lemmers RFH AD - Department of Internal Medicine, Section Pharmacology and Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. AD - Maxima Medical Center, Internal Medicine, Eindhoven, the Netherlands. FAU - Martens, N E M A AU - Martens NEMA AD - Department of Internal Medicine, Section Pharmacology and Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Maas, A H AU - Maas AH AD - Maxima Medical Center, Internal Medicine, Eindhoven, the Netherlands. FAU - van Vark-van der Zee, L C AU - van Vark-van der Zee LC AD - Department of Internal Medicine, Section Pharmacology and Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Leijten, F P J AU - Leijten FPJ AD - Department of Internal Medicine, Section Pharmacology and Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Groot-van Ruijven, C M AU - Groot-van Ruijven CM AD - Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - van Hoek, M AU - van Hoek M AD - Department of Internal Medicine, Section Pharmacology and Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Lieverse, A G AU - Lieverse AG AD - Maxima Medical Center, Internal Medicine, Eindhoven, the Netherlands. FAU - Sijbrands, E J G AU - Sijbrands EJG AD - Department of Internal Medicine, Section Pharmacology and Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Haak, H R AU - Haak HR AD - Maxima Medical Center, Internal Medicine, Eindhoven, the Netherlands. FAU - Leenen, P J M AU - Leenen PJM AD - Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Verhoeven, A J M AU - Verhoeven AJM AD - Department of Internal Medicine, Section Pharmacology and Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Dik, W A AU - Dik WA AD - Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands. AD - Laboratory Medical Immunology, Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Mulder, M T AU - Mulder MT AD - Department of Internal Medicine, Section Pharmacology and Vascular Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. LA - eng PT - Journal Article DEP - 20210824 PL - Netherlands TA - Atheroscler Plus JT - Atherosclerosis plus JID - 9918249514806676 PMC - PMC9833245 OTO - NOTNLM OT - Breakfast OT - Density gradient centrifugation OT - Endothelium OT - High-density lipoprotein function OT - Type 2 diabetes mellitus OT - VCAM-1 COIS- The authors declare that they have no conflict of interest. EDAT- 2021/08/24 00:00 MHDA- 2021/08/24 00:01 PMCR- 2021/08/24 CRDT- 2023/01/16 03:07 PHST- 2021/05/03 00:00 [received] PHST- 2021/07/26 00:00 [revised] PHST- 2021/08/18 00:00 [accepted] PHST- 2023/01/16 03:07 [entrez] PHST- 2021/08/24 00:00 [pubmed] PHST- 2021/08/24 00:01 [medline] PHST- 2021/08/24 00:00 [pmc-release] AID - S2667-0895(21)00028-6 [pii] AID - 10.1016/j.athplu.2021.08.006 [doi] PST - epublish SO - Atheroscler Plus. 2021 Aug 24;44:43-50. doi: 10.1016/j.athplu.2021.08.006. eCollection 2021 Oct.