Vissenaekens Hanne, Grootaert Charlotte, Raes Katleen, De Munck Julie, Smagghe Guy, Boon Nico, Van Camp John
Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium.
Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium.
Inflammation. 2022 Aug;45(4):1600-1611. doi: 10.1007/s10753-022-01645-w. Epub 2022 Mar 30.
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.
动脉粥样硬化的起始与内皮细胞的促炎状态有关。槲皮素是一种大量存在于植物性食物中的类黄酮，可能对心血管健康产生影响。在本研究中，研究了槲皮素对脂多糖（LPS）介导的内皮炎症以及单核细胞黏附与迁移的影响，这些都是动脉粥样硬化形成过程的起始步骤。新型体外多细胞模型模拟了肠道-内皮-单核细胞/巨噬细胞轴，能够将相关的肠道类黄酮吸收、代谢和外排，以及随后对外周内皮细胞的生物活性结合起来。在这种三重共培养中，槲皮素的暴露减少了单核细胞对LPS应激内皮的黏附以及巨噬细胞通过该内皮的迁移，这与可溶性血管细胞黏附分子-1（sVCAM-1）水平显著降低有关。此外，在LPS诱导的内皮激活方面，槲皮素降低了促炎细胞环境，表现为肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和sVCAM-1的表达降低。这些发现突出了一种作用模式，即就槲皮素浓度、代谢产物和细胞间相互作用而言，槲皮素可能在更符合生理条件的情况下对动脉粥样硬化的初始状态产生积极影响。
