Abstract
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, is recognized as a critical regulator in physiological and pathophysiological processes of atherosclerosis (AS). However, the underlying mechanism remains unclear. As the precursor cells of endothelial cells (ECs), endothelial progenitor cells (EPCs) can prevent AS development through repairing endothelial monolayer impaired by proatherogenic factors. The present study investigated the effects of S1P on the biological features of mouse bone marrow-derived EPCs and the underlying mechanism. The results showed that S1P improved cell viability, adhesion, and nitric oxide (NO) release of EPCs in a bell-shaped manner, and migration and tube formation dose-dependently. The aforementioned beneficial effects of S1P on EPCs could be inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor of LY294002 and nitric oxide synthase (NOS) inhibitor of N’-nitro-L-arginine-methyl ester hydrochloride (L-NAME). The inhibitor of LY294002 inhibited S1P-stimulated activation of phosphorylated protein kinase B (AKT) (p-AKT) and endothelial nitric oxide synthase (eNOS) (p-eNOS), and down-regulated the level of eNOS significantly. The results suggest that S1P improves the biological features of EPCs partially through PI3K/AKT/eNOS/NO signaling pathway.
Highlights
The impairment in vascular endothelial function induced by risk factors, is an important initial event for the onset and progression of atherosclerosis (AS) [1]
After being isolated and cultured in an endothelial growth medium-2 MV (EGM-2MV) medium for seven days at 37 ◦ C with 5% CO2, mononuclear cells (MNCs) derived from mouse bone marrow showed cobblestone-like morphology (Figure 1a)
The mononuclear (MNCs) isolated frombone mousemarrow bone marrow showthe characteristics ofofEPCs mononuclear cells (MNCs)cells isolated from mouse showthe characteristics
Summary
The impairment in vascular endothelial function induced by risk factors (such as hypertension, hyperlipidemia, and hyperglycemia), is an important initial event for the onset and progression of atherosclerosis (AS) [1]. Endothelial progenitor cells (EPCs) derived from peripheral blood or bone marrow can differentiate into mature endothelial cells (ECs) and migrate to injured sites to promote endothelium repair and neovascularization in the vessel wall, and preventing AS progression [2,3,4]. It is reported that EPCs in AS patients fail to repair the injured endothelium, which breaks the physiological equilibrium between endothelial damage and regeneration. Molecules 2019, 24, 2404 proliferation, migration, adhesion, tube formation, and nitric oxide (NO) production of EPCs is conducive to repair the injured endothelial monolayer [5,6], and inhibiting the initiation and progression of AS. S1P mediates various activities including cardioprotection following ischemia/reperfusion injury, anti-inflammation, endothelial function improvement, anti-oxidation, anti-AS, and antithrombus [9,10].
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