Ecklonia Cava Extract Attenuates Endothelial Cell Dysfunction by Modulation of Inflammation and Brown Adipocyte Function in Perivascular Fat Tissue

Abstract

It is well known that perivascular fat tissue (PVAT) dysfunction can induce endothelial cell (EC) dysfunction, an event which is related with various cardiovascular diseases. In this study, we evaluated whether Ecklonia cava extract (ECE) and pyrogallol-phloroglucinol-6,6-bieckol (PPB), one component of ECE, could attenuate EC dysfunction by modulating diet-induced PVAT dysfunction mediated by inflammation and ER stress. A high fat diet (HFD) led to an increase in the number and size of white adipocytes in PVAT; PPB and ECE attenuated those increases. Additionally, ECE and PPB attenuated: (i) an increase in the number of M1 macrophages and the expression level of monocyte chemoattractant protein-1 (MCP-1), both of which are related to increases in macrophage infiltration and induction of inflammation in PVAT, and (ii) the expression of pro-inflammatory cytokines (e.g., tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, chemerin) in PVAT which led to vasoconstriction. Furthermore, ECE and PPB: (i) enhanced the expression of adiponectin and IL-10 which had anti-inflammatory and vasodilator effects, (ii) decreased HFD-induced endoplasmic reticulum (ER) stress and (iii) attenuated the ER stress mediated reduction in sirtuin type 1 (Sirt1) and peroxisome proliferator-activated receptor gamma (PPAR gamma) expression. Protective effects against decreased Sirt1 and PPAR gamma expression led to the restoration of uncoupling protein-1 (UCP-1) expression and the browning process in PVAT. PPB or ECE attenuated endothelial dysfunction by enhancing the pAMPK-PI3K-peNOS pathway and reducing the expression of endothelin-1 (ET-1). In conclusion, PPB and ECE attenuated PVAT dysfunction and subsequent endothelial dysfunction by: (i) decreasing inflammation and ER stress, and (ii) modulating brown adipocyte function.