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

Abstract

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.

• Authors: Kun Ren, Yan-Ju Lu, Zhong-Cheng Mo, Xing -Liu, Zhen-Li Tang, Yue Jiang, Xiao-Shan Peng, Li Li, Qing-Hai Zhang, Guang-Hui Yi
• Journal: Journal of physiology and biochemistry (J Physiol Biochem) Vol. 73 Issue 2 Pg. 287-296 (May 2017) ISSN: 1877-8755 [Electronic] Spain
• PMID: 28181168 (Publication Type: Journal Article)

Chemical References

• 2-hexyl-1-cyclopentanone thiosemicarbazone
• APOA1 protein, human
• Apolipoprotein A-I
• Cyclopentanes
• IL10 protein, human
• IL1B protein, human
• Interleukin-1beta
• Lipoproteins, LDL
• Lysophospholipids
• Receptors, Lysosphingolipid
• Recombinant Proteins
• S1PR2 protein, human
• SCARB1 protein, human
• Scavenger Receptors, Class B
• Sphingosine-1-Phosphate Receptors
• TNF protein, human
• Thiosemicarbazones
• Tumor Necrosis Factor-alpha
• oxidized low density lipoprotein
• Interleukin-10
• sphingosine 1-phosphate
• Phosphatidylinositol 3-Kinase
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• Sphingosine

Topics

• Active Transport, Cell Nucleus (drug effects)
• Apolipoprotein A-I (genetics, metabolism)
• Cells, Cultured
• Cyclopentanes (pharmacology)
• Endothelium, Vascular (cytology, drug effects, immunology, metabolism)
• Gene Expression Regulation (drug effects)
• Human Umbilical Vein Endothelial Cells (cytology, drug effects, immunology, metabolism)
• Humans
• Interleukin-10 (agonists, metabolism)
• Interleukin-1beta (agonists, metabolism)
• Kinetics
• Lipoproteins, LDL (adverse effects, genetics, metabolism)
• Lysophospholipids (metabolism)
• Phosphatidylinositol 3-Kinase (metabolism)
• Proto-Oncogene Proteins c-akt (agonists, metabolism)
• Receptors, Lysosphingolipid (agonists, genetics, metabolism)
• Recombinant Proteins (chemistry, metabolism)
• Scavenger Receptors, Class B (agonists, antagonists & inhibitors, genetics, metabolism)
• Signal Transduction (drug effects)
• Sphingosine (analogs & derivatives, metabolism)
• Sphingosine-1-Phosphate Receptors
• Thiosemicarbazones (pharmacology)
• Tumor Necrosis Factor-alpha (agonists, metabolism)