AUTHOR=Xiang Debiao , Li Yamei , Cao Yuling , Huang Ying , Zhou Lili , Lin Xiulian , Qiao Yong , Li Xin , Liao Duanfang 

TITLE=Different Effects of Endothelial Extracellular Vesicles and LPS-Induced Endothelial Extracellular Vesicles on Vascular Smooth Muscle Cells: Role of Curcumin and Its Derivatives

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.649352

DOI=10.3389/fcvm.2021.649352

ISSN=2297-055X

ABSTRACT=Abstract: Background: Atherosclerosis (AS) is a progressive vascular wall disease characterized by abnormal accumulation of lipids and immune cells in the blood vessel wall. It is the primary pathological process of various cardiovascular and cerebrovascular diseases, such as myocardial infarction, angina pectoris, heart failure, stroke, etc. As one of the main focal cells, vascular endothelial cell function is of great significance in atherosclerosis. Purpose: To improve the anti-atherosclerotic effect of curcumin, Nicotinic-curcumin was obtained through chemical structural modification. 
Methods: Nicotinic-curcumin (NC) was obtained by esterification, and its chemical structure was identified using NMR and MS. In-vitro, anti-inflammatory effects of NC were studied using human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS) as an inflammatory injury model. Exosomes secreted by HUVECs were isolated by ultra-high centrifugation. The exosome secretion and its miRNA level were quantified after LPS stimulation and NC treatment of HUVECs. The effect of endothelial exosomes on vascular smooth muscle cell function was evaluated including proliferation, migration and lipid accumulation.
Results: Nicotinic-curcumin (NC) was synthesized effectively with purity above 97%. In-vitro, LPS induced increased secretion of exosomes in HUVECs. NC treatment effectively inhibited HUVECs inflammation and reduced LPS-induced exosome secretion compared with the model group. After LPS stimulation, the levels of miRNA-142-3p and miRNA-126-3p increased while miRNA-143-3p declined in exosomes secreted by HUVECs. NC treatment could effectively reduce the levels of change of miRNAs. Endothelial exosomes had a protective effect on vascular smooth muscle cells, while LPS-induced exosomes were not or even harmful.
Conclusion: Thus, Nicotinic-curcumin (NC) can inhibit endothelial cell inflammation and reducing the release of pro-inflammatory cytokines by exosomes. Compared with endothelial exosomes, the effect of LPS-induced exosomes on vascular smooth muscle cell may be related to the change of contents in exosomes.