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Nutrients 2018, 10(2), 172; doi:10.3390/nu10020172

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

1
Department of Human Genetics and Einthoven Laboratory for Experimental Medicine, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands
2
Department of Surgery and Einthoven Laboratory for Experimental Medicine, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands
3
Department of Medicine, Division Endocrinology, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands
*
Authors to whom correspondence should be addressed.
Received: 3 January 2018 / Revised: 25 January 2018 / Accepted: 25 January 2018 / Published: 3 February 2018
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Abstract

The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol. View Full-Text
Keywords: atherosclerosis; inulin; prebiotics; APOE*3-Leiden mice; cholesterol; remodeling atherosclerosis; inulin; prebiotics; APOE*3-Leiden mice; cholesterol; remodeling
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hoving, L.R.; de Vries, M.R.; de Jong, R.C.M.; Katiraei, S.; Pronk, A.; Quax, P.H.A.; van Harmelen, V.; Willems van Dijk, K. The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice. Nutrients 2018, 10, 172.

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