(P11-06-26) Anthocyanin-Derived Phase II and Microbial Metabolites Protect Brain Endothelium and Mesenteric Vessel Reactivity Through Multigenomic Modulation

Objectives: Endothelial dysfunction induced by inflammatory stimuli can be detrimental to vascular health in contribution to neurocognitive and cardiovascular disease development, which may be mediated by the consumption of anthocyanin-rich diets. The interplay between anthocyanin metabolism and their vasoprotective effects against neuroinflammation via nutrigenomic mechanisms remains of widespread interest. Therefore, this study aimed to uncover the molecular pathways of anthocyanin-mediated action against proinflammatory (neuro)vascular stress across the gut-brain axis.

Methods: Human brain microvascular endothelial cells (HBMECs) were pretreated with phase II or gut microbiome-derived anthocyanin metabolites before TNF-α exposure. Global transcriptomic changes of HBMECs were determined via genomic microarrays and comprehensive bioinformatic analysis of coding and non-coding genes. Additionally, ex vivo second order mesenteric arteries isolated from C57BL/6 mice were identically incubated with anthocyanin metabolites prior to lipopolysaccharide (LPS)-induced stress to assess vascular reactivity via wire myography. Isometric force of vasoconstriction and vasodilation were measured in response to phenylephrine and acetylcholine, respectively, following treatment with anthocyanin metabolites and LPS.

Results: Pretreatment of anthocyanin metabolites impeded inflammatory-related (neuro)vascular endothelial dysfunction. The neuroprotection in the HBMECs was driven by differential modulation of coding and non-coding (miRNAs, lncRNAs, snoRNAs, circRNAs) genetic expression, indicative of multi-genomic influence by dietary anthocyanins. Integrative bioinformatic analysis revealed that coding genes and targets of non-coding genes regulated by anthocyanin metabolites were involved in pathways of cell cycle management, cell-cell permeability, and neutrophil migration. Furthermore, pretreatment of anthocyanin metabolites alleviated LPS-induced vascular hyper-reactivity in the murine mesenteric arteries.

Conclusions: Results indicated that anthocyanin metabolites improved endothelial functionality, such as blood-brain barrier protection and vasorelaxation, under inflammatory stress via multi-genomic interactions.

Funding Sources: N/A