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Lysophosphatidylcholine enhances cytokine production of endothelial cells via induction of L-type amino acid transporter 1 and cell surface antigen 4F2
- Source :
- Arteriosclerosis, thrombosis, and vascular biology. 24(9)
- Publication Year :
- 2004
-
Abstract
- Objective— A diverse range of lipid oxidation products detected in oxidized low-density lipoprotein (oxLDL) and atherosclerotic lesions are capable of eliciting biological responses in vascular cells. We performed DNA microarray experiments to explore novel responses of human umbilical vein endothelial cells (HUVECs) to oxLDL and its components. Methods and Results— cDNA microarray analysis showed that oxLDL, lysophosphatidylcholine (LysoPC), 4-hydroxy-2-nonenal, and oxysterols altered gene expression specifically, but some genes were commonly induced in HUVECs. Solute carrier family 3 member 2 and family 7 member 5, encoding the heavy chain of the cell surface antigen 4F2 (4F2hc) and the L-type amino acid transporter 1 (LAT1), respectively, were induced by oxLDL and many oxidation products. LAT1 requires 4F2hc to form a heterodimeric functional complex to transport neutral amino acids into the cell. LysoPC increased membrane protein levels of LAT1 confirmed by Western blot analysis and also uptake of L-[ 14 C]leucine, which was inhibited by a competitive inhibitor for LAT1. The release of interleukin 6 (IL-6) and IL-8 was increased in LysoPC-treated cells and was attenuated by the LAT1 inhibitor. Conclusions— These findings suggest that an increase in uptake of neutral amino acids induced by LysoPC results in enhancement of inflammatory responses of endothelial cells.
- Subjects :
- Umbilical Veins
Fusion Regulatory Protein 1, Heavy Chain
Arteriosclerosis
medicine.medical_treatment
Cell
Fusion Regulatory Protein-1
Biology
Large Neutral Amino Acid-Transporter 1
chemistry.chemical_compound
Mice
Lipid oxidation
medicine
Animals
Humans
Amino acid transporter
Aorta
Cells, Cultured
Inflammation
Mice, Knockout
Endothelial Cells
Lysophosphatidylcholines
Solute carrier family
Endothelial stem cell
Lipoproteins, LDL
Lysophosphatidylcholine
medicine.anatomical_structure
Cytokine
chemistry
Biochemistry
Gene Expression Regulation
Receptors, LDL
Cytokines
Endothelium, Vascular
Lipid Peroxidation
Leucine
Cardiology and Cardiovascular Medicine
Dimerization
Subjects
Details
- ISSN :
- 15244636
- Volume :
- 24
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Accession number :
- edsair.doi.dedup.....e5dd827d6108470bf910e7ba3025da95