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Quercetin Mitigates Endothelial Activation in a Novel Intestinal-Endothelial-Monocyte/Macrophage Coculture Setup

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Abstract—

Atherosclerosis initiation is associated with a pro-inflammatory state of the endothelium. Quercetin is a flavonoid abundantly present in plant-based foods, with a possible impact on cardiovascular health. In this study, the effects of quercetin on lipopolysaccharide (LPS)-mediated endothelial inflammation and monocyte adhesion and migration, which are initial steps of the atherogenic process, are studied. Novel in vitro multicellular models simulating the intestinal-endothelial-monocytes/macrophages axis allowed to combine relevant intestinal flavonoid absorption, metabolism and efflux, and the consequent bioactivity towards peripheral endothelial cells. In this triple coculture, quercetin exposure decreased monocyte adhesion to and macrophage migration through an LPS-stressed endothelium, and this was associated with significantly lower levels of soluble vascular cell adhesion molecule-1 (sVCAM-1). Furthermore, quercetin decreased the pro-inflammatory cell environment upon LPS-induced endothelial activation, in terms of tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and sVCAM-1 expression. These findings highlight a mode-of-action by which quercetin may positively impact the initial states of atherosclerosis under more physiologically relevant conditions in terms of quercetin concentrations, metabolites, and intercellular crosstalk.

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Funding

Hanne Vissenaekens is holder of a doctoral (PhD) grant Strategic Basic Research (SB) of Research Foundation-Flanders (FWO-Vlaanderen; 1S18417N). The authors would like to thank BOF (01B04212) for the funding of the automated TEER equipment (REMS) and flow cytometer.

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Authors and Affiliations

  1. Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium

    Hanne Vissenaekens, Charlotte Grootaert, Katleen Raes, Julie De Munck & John Van Camp

  2. Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium

    Hanne Vissenaekens & Guy Smagghe

  3. Center for Microbial Ecology and Technology (CMET), Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium

    Nico Boon

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  1. Hanne Vissenaekens
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Contributions

Conceptualization: Hanne Vissenaekens, Charlotte Grootaert, Katleen Raes, Guy Smagghe, John Van Camp. Data curation: Hanne Vissenaekens. Formal analysis: Hanne Vissenaekens. Funding acquisition: Hanne Vissenaekens, Charlotte Grootaert, Katleen Raes, Guy Smagghe, John Van Camp. Investigation: Hanne Vissenaekens, Julie De Munck. Methodology: Hanne Vissenaekens, Charlotte Grootaert, Nico Boon. Project administration: Charlotte Grootaert, Katleen Raes, Guy Smagghe, John Van Camp. Resources: Nico Boon, Katleen Raes, Guy Smagghe, John Van Camp. Software: Hanne Vissenaekens. Supervision: Katleen Raes, Guy Smagghe, John Van Camp. Validation: Hanne Vissenaekens, Charlotte Grootaert. Visualization: Hanne Vissenaekens, Charlotte Grootaert. Writing-original draft: Hanne Vissenaekens. Writing-review and editing: Charlotte Grootaert, Katleen Raes, Julie De Munck, Guy Smagghe, Nico Boon, John Van Camp.

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Vissenaekens, H., Grootaert, C., Raes, K. et al. Quercetin Mitigates Endothelial Activation in a Novel Intestinal-Endothelial-Monocyte/Macrophage Coculture Setup. Inflammation 45, 1600–1611 (2022). https://doi.org/10.1007/s10753-022-01645-w

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