Journal Article

ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs

Jiang, Yue, Peng, Xiao-Shan, Liu, Xing, Li, Li, Ren, Kun, Lu, Yan-Ju, Zhang, Qing-Hai, Mo, Zhong-Cheng, Yi, Guang-Hui, Tang, Zhen-Li

2017

Overview

Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Scavenger receptor class B member I (SR-BI), a high-affinity receptor for apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL), inhibits nuclear factor-κB (NF-κB) translocation and decreases the plasma levels of inflammatory mediators via the PI3K/Akt pathway. We hypothesized that the inflammatory effects of S1P/S1PR2 on ECs may be regulated by apoA-I/SR-BI. The results showed that ox-LDL, a pro-inflammatory factor, augmented the S1PR2 level in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. In addition, S1P/S1PR2 signaling influenced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, aggravating inflammation in HUVECs. Moreover, the pro-inflammatory effects induced by S1P/S1PR2 were attenuated by SR-BI overexpression and enhanced by an SR-BI inhibitor, BLT-1. Further experiments showed that the PI3K/Akt signaling pathway was involved in this process. Taken together, these results demonstrate that apoA-I/SR-BI negatively regulates S1P/S1PR2-mediated inflammation in HUVECs by activating the PI3K/Akt signaling pathway.

• Publisher: Springer Netherlands,Springer Nature B.V
• Subject: 1-Phosphatidylinositol 3-kinase / Active Transport, Cell Nucleus - drug effects / AKT protein / Animal Physiology / Antibiotics / Antibodies / Apolipoprotein A / Apolipoprotein A-I / Apolipoprotein A-I - genetics / Apolipoprotein A-I - metabolism / Arteriosclerosis / Atherosclerosis / Biomedical and Life Sciences / Biomedicine / Blood vessels / Cell adhesion & migration / Cells, Cultured / Cholesterol / Cyclopentanes - pharmacology / Density / Endothelial cells / Endothelium, Vascular - cytology / Endothelium, Vascular - drug effects / Endothelium, Vascular - immunology / Endothelium, Vascular - metabolism / Gene Expression Regulation - drug effects / Glucose / High density lipoprotein / Human Physiology / Human Umbilical Vein Endothelial Cells - cytology / Human Umbilical Vein Endothelial Cells - drug effects / Human Umbilical Vein Endothelial Cells - immunology / Human Umbilical Vein Endothelial Cells - metabolism / Humans / Inflammation / Interleukin 10 / Interleukin-10 - agonists / Interleukin-10 - metabolism / Interleukin-1beta - agonists / Interleukin-1beta - metabolism / Kinases / Kinetics / Lipoproteins, LDL - adverse effects / Lipoproteins, LDL - genetics / Lipoproteins, LDL - metabolism / Low density lipoprotein / Lysophospholipids - metabolism / NF-κB protein / Original Article / Penicillin / Phosphatidylinositol / Phosphatidylinositol 3-Kinase - metabolism / Plasma levels / Proteins / Proto-Oncogene Proteins c-akt - agonists / Proto-Oncogene Proteins c-akt - metabolism / Receptors / Receptors, Lysosphingolipid - agonists / Receptors, Lysosphingolipid - genetics / Receptors, Lysosphingolipid - metabolism / Recombinant Proteins - chemistry / Recombinant Proteins - metabolism / Scavenger receptors / Scavenger Receptors, Class B - agonists / Scavenger Receptors, Class B - antagonists & inhibitors / Scavenger Receptors, Class B - genetics / Scavenger Receptors, Class B - metabolism / Signal transduction / Signal Transduction - drug effects / Sphingosine - analogs & derivatives / Sphingosine - metabolism / Sphingosine 1-phosphate / Thiosemicarbazones - pharmacology / Tumor Necrosis Factor-alpha - agonists / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Umbilical vein