Juglanin suppresses oscillatory shear stress-induced endothelial dysfunction: An implication in atherosclerosis.
INTRODUCTION
Atherosclerosis is characterized by endothelial cell dysfunction followed by lesion formation, arterial stenosis, potentially arterial occlusion, and severe outcomes. Novel treatments to slow or prevent the progression of the disease are of considerable clinical value. In the present study, we investigated the potential anti-atherosclerotic effects of the natural product juglanin in oscillatory shear stress (OSS) exposed endothelial cells.


METHODS
Human aortic endothelial cells (HAECs) were exposed to OSS generated by a micro fluidal Teflon cone at 1 Hz frequency cycles (±5 dyn/cm2) in the presence or absence of 2.5 and 5 μM juglanin for 24 h. The expression levels of inflammatory factors and vascular adhesion molecules were evaluated using qRT-PCR, Western Blot, and ELISA. DHE assay was used to detect the production of ROS. The monocytic THP-1 cells were labeled with calcein-AM and incubated with HAECs for adhesion assay.


RESULTS
Juglanin reduces OSS-induced oxidative stress by reducing the production of ROS through downregulation of NOX-2 and rescuing OSS-induced reduced expression of eNOS. Juglanin also inhibits the inflammatory response by suppressing OSS-induced expressions of IL-1β, MCP-1, and HMGB1. Using THP-1 monocytes, we show that juglanin reduces the attachment of monocytes to endothelial cells by inhibiting the expression of VCAM-1 and E-selectin. Moreover, Juglanin rescues OSS-reduced expression of atheroprotective transcriptional factor KLF2.


CONCLUSIONS
Our findings indicate that juglanin protects against various atheroprone OSS-induced endothelial dysfunction. Juglanin has potential implication as a candidate for vascular intervention of atherosclerosis.
['Zhao|Jian|J|', 'Quan|Xiaoqiang|X|', 'Xie|Zhouliang|Z|', 'Zhang|Leilei|L|', 'Ding|Zhiwei|Z|']
D050197:Atherosclerosis D002448:Cell Adhesion D015815:Cell Adhesion Molecules D018920:Coculture Techniques D016207:Cytokines D042783:Endothelial Cells D006027:Glycosides D006801:Humans D018836:Inflammation Mediators D044949:Kaempferols D040542:Mechanotransduction, Cellular D009000:Monocytes D018384:Oxidative Stress D011673:Pulsatile Flow D017382:Reactive Oxygen Species D013314:Stress, Mechanical D000074084:THP-1 Cells
Juglanin Oscillatory shear stress (OSS) KLF2 Cardiovascular disease Inflammation