Curcumin Alleviates Palmitic Acid-Induced LOX-1 Upregulation by Suppressing Endoplasmic Reticulum Stress in HUVECs.

Ruixi Luo,Lifeng Zhao,Shuaishuai Li,Kun Cai,Weiyi Tian,Honghong Yu,La Wang,Qi Yu,Peng Chen,Christos K Kontos

doi:10.1155/2021/9983725

Abstract

Excessive free fatty acid- (FFA-) induced endothelial lipotoxicity is involved in the pathogenesis of atherosclerosis. Endoplasmic reticulum (ER) stress is mechanistically related to endothelial lipotoxicity. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major oxidatively modified low-density lipoprotein (OxLDL) receptor in endothelial cells and is highly abundant in atherosclerotic lesions. Curcumin reduces the LOX-1 expression; however, the mechanism underlying this effect remains unknown. In the current study, we explored whether curcumin ameliorates palmitic acid- (PA-) induced endothelial lipotoxicity and LOX-1 upregulation by reducing ER stress in human umbilical vein endothelial cells (HUVECs). We built endothelial lipotoxicity in vitro and found that LOX-1 was upregulated after PA stimulation, during which ER stress played an important role. Next, we observed that curcumin substantially alleviated PA-induced lipotoxicity by restoring cell viability, increasing angiogenesis, and decreasing lipid deposition. Furthermore, LOX-1 upregulation in HUVECs was blocked by curcumin, possibly via ER stress suppression. Overall, our findings demonstrated that curcumin alleviates endothelial lipotoxicity and LOX-1 upregulation, and ER stress inhibition may play a critical role in this effect.

Highlights

Current hypotheses suggest that high levels of free fatty acids (FFAs) are a risk factor for the pathology of atherosclerosis (AS) [1]
In this study, we examined whether curcumin ameliorates the palmitic acid- (PA-)induced lipoprotein receptor-1 (LOX-1) expression in primary endothelial cells and how Endoplasmic reticulum (ER) stress is modulated by curcumin
Because ER stress contributes to LOX-1 upregulation caused by palmitic acid (PA) and curcumin suppresses the LOX-1 expression, we investigated whether curcumin inhibits PA-induced ER stress in human umbilical vein endothelial cells (HUVECs)

Summary

Introduction

Current hypotheses suggest that high levels of free fatty acids (FFAs) are a risk factor for the pathology of atherosclerosis (AS) [1]. Endothelial cell dysfunction, which is the innermost layer of blood vessels, is considered an early indicator of AS [2]. We showed that palmitic acid (PA) induces lipotoxicity in endothelial cells [3], which contributes to the early phase of AS pathogenesis. The roles and detailed mechanisms of FFAs in the pathogenesis of AS remain unclear. Excessive binding of Ox-LDL to LOX-1 induces endothelial dysfunction, initiating atherosclerosis [5, 6]. Preventing PA-induced lipotoxicity and LOX-1 upregulation in endothelial cells will contribute to avoiding endothelial damage

Methods

Results

Conclusion