Abstract
Apelin receptor (APJ) deficiency has been reported to be preventive against atherosclerosis. However, the mechanism of this effect remains unknown. In this study, quantitative real-time RT-PCR, Western blotting and ELISA analyses revealed a significant increase in the expression of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) treated with apelin. Inhibitors of cellular signal transduction molecules were used to demonstrate involvement of nuclear factor kappa-B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways in apelin-APJ-induced activation of adhesion molecules and chemokines. Inhibition of APJ expression by RNA interference abrogated apelin-induced expression of adhesion molecules and chemokines and apelin-stimulated cellular signal transduction in HUVECs. The apelin-APJ system in endothelial cells is involved in the expression of adhesion molecules and chemokines, which are important for the initiation of endothelial inflammation-related atherosclerosis. Therefore, apelin-APJ and the cell signaling pathways activated by this system in endothelial cells may represent targets for therapy of atherosclerosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apelin
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Apelin Receptors
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Blotting, Western
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Cells, Cultured
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Chemokine CCL2 / genetics*
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Chemokine CCL2 / metabolism
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Enzyme-Linked Immunosorbent Assay
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Gene Expression Regulation / drug effects
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Human Umbilical Vein Endothelial Cells / cytology
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Human Umbilical Vein Endothelial Cells / drug effects*
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Human Umbilical Vein Endothelial Cells / metabolism
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Humans
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Intercellular Adhesion Molecule-1 / genetics*
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Intercellular Adhesion Molecule-1 / metabolism
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Intercellular Signaling Peptides and Proteins / pharmacology*
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JNK Mitogen-Activated Protein Kinases / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / genetics
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NF-kappa B / metabolism
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Receptors, G-Protein-Coupled / antagonists & inhibitors
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Receptors, G-Protein-Coupled / genetics*
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Receptors, G-Protein-Coupled / metabolism
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Signal Transduction / drug effects
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Vascular Cell Adhesion Molecule-1 / genetics*
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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APLN protein, human
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APLNR protein, human
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Apelin
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Apelin Receptors
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CCL2 protein, human
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Chemokine CCL2
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Intercellular Signaling Peptides and Proteins
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NF-kappa B
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RNA, Small Interfering
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Receptors, G-Protein-Coupled
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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JNK Mitogen-Activated Protein Kinases