EVOO Promotes a Less Atherogenic Profile Than Sunflower Oil in Smooth Muscle Cells Through the Extracellular Vesicles Secreted by Endothelial Cells

Abstract

BackgroundLittle is known about the effect of extra virgin olive (EVOO) and sunflower oil (SO) on the composition of extracellular vesicles (EVs) secreted by endothelial cells and the effects of these EVs on smooth muscle cells (SMCs). These cells play an important role in the development of atherosclerosis.MethodsWe evaluated the effects of endothelial cells-derived EVs incubated with triglyceride-rich lipoproteins obtained after a high-fat meal with EVOO (EVOO-EVs) and SO (SO-EVs), on the transcriptomic profile of SMCs.ResultsWe found 41 upregulated and 19 downregulated differentially expressed (DE)-miRNAs in EVOO-EVs. Afterwards, SMCs were incubated with EVOO-EVs and SO-EVs. SMCs incubated with SO-EVs showed a greater number of DE-mRNA involved in pathways related to cancer, focal adhesion, regulation of actin cytoskeleton, and MAPK, toll-like receptor, chemokine and Wnt signaling pathways than in SMCs incubated with EVOO-EVs. These DE-mRNAs were involved in biological processes related to the response to endogenous stimulus, cell motility, regulation of intracellular signal transduction and cell population proliferation.ConclusionEVOO and SO can differently modify the miRNA composition of HUVEC-derived EVs. These EVs can regulate the SMCs transcriptomic profile, with SO-EVs promoting a profile more closely linked to the development of atherosclerosis than EVOO-EVs.

Extracellular vesicles in atherosclerosis and vascular calcification: the versatile non-coding RNAs from endothelial cells and vascular smooth muscle cells

“…MiR-19b encapsulated in HUVECs-EVs mentioned above ( 52 ), the previous name of miR-19b-3p, reduced HUVECs migration and damaged lymphatic system function by negatively regulating TGF-βRII expression ( 56 , 76 ). MiR-19b-3p in endothelial microparticles (MPs) exaggerated AS by targeting the suppressor of cytokine signaling 3 (SOCS3) ( 77 ).…”

“…Xiang et al ( 51 ) performed miRNA-Seq analysis and found that EVs derived from lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) promoted human aortic smooth muscle cell (HASMC) proliferation and migration, in which four upregulated miRNAs (including miR-27a-3p, miR-126-5p, miR-155-5p, and miR-365b-3p) and nine downregulated miRNAs (including let-7b-5p, miR-10a-5p, miR-10b-5p, miR-21-3p, miR-30a-5p, miR-92a-3p, miR-125a-3p, miR-143-3p, and miR-181a-2-3p) participated in various aspects of atherosclerotic lesion formation. In another RNA-seq research, a significant upregulation of 49 miRNAs (including miR-19b-3p and miR-126-5p) and downregulation of 19 miRNAs in extra-virgin olive-induced HUVECs-EVs compared to sunflower oil-induced HUVECs-EVs were observed, which closely linked to the development of AS ( 52 ). The finding of higher expression of miR-126-5p was detected in both studies ( 51 , 52 ).…”

“…In another RNA-seq research, a significant upregulation of 49 miRNAs (including miR-19b-3p and miR-126-5p) and downregulation of 19 miRNAs in extra-virgin olive-induced HUVECs-EVs compared to sunflower oil-induced HUVECs-EVs were observed, which closely linked to the development of AS ( 52 ). The finding of higher expression of miR-126-5p was detected in both studies ( 51 , 52 ). It is no coincidence that miR-126-5p was found to have a linear relationship with coronary calcium in outpatients with AS ( 53 ).…”

“…It has been shown that miRNAs encapsulated in EC-EVs exerted atheroprotective or proatherogenic function in several studies. The differential expression of miRNAs encapsulated in EC-EVs during AS was analyzed by miRNA-Sequence (miRNA-seq) ( 51 , 52 ), providing a reasonable prospect to illuminate the detailed mechanisms miRNAs are involved in. Here, miRNAs encapsulated in EC-EVs including miR-92a-3p, miR-155-5p, miR-505-3p, miR-19b-3p, and miR-4306 promoted AS, while miR-126-5p and miR-145-5p inhibited AS process ( 53 – 61 ).…”