CC-Chemokine Ligand 2 (CCL2) Suppresses High Density Lipoprotein (HDL) Internalization and Cholesterol Efflux via CC-Chemokine Receptor 2 (CCR2) Induction and p42/44 Mitogen-activated Protein Kinase (MAPK) Activation in Human Endothelial Cells
| Autor: | Wei-Bin Cai, Shu-Xian Zhou, Jinlan Bao, Runlu Sun, Jieyu Jiang, Bo Zhang, Yu-Ling Zhang, Hong Wang, Can-Xia Huang, Jing-Feng Wang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male CCR2 medicine.medical_specialty MAP Kinase Signaling System Receptors CCR2 media_common.quotation_subject Coronary Artery Disease 030204 cardiovascular system & hematology Biology Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Human Umbilical Vein Endothelial Cells Humans mitogen-activated protein kinase (MAPK) Internalization Protein kinase A Molecular Biology Chemokine CCL2 media_common Mitogen-Activated Protein Kinase 1 CC-chemokine ligand 2 (CCL2) Mitogen-Activated Protein Kinase 3 Apolipoprotein A-I Cholesterol Reverse cholesterol transport Cell Biology Lipids Endothelial stem cell Enzyme Activation 030104 developmental biology Endocrinology high-density lipoprotein (HDL) chemistry Gene Expression Regulation cholesterol metabolism endothelial cell lipids (amino acids peptides and proteins) Female atherosclerosis CC chemokine receptors Lipoproteins HDL |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Popis: | High density lipoprotein (HDL) has been proposed to be internalized and to promote reverse cholesterol transport in endothelial cells (ECs). However, the mechanism underlying these processes has not been studied. In this study, we aim to characterize HDL internalization and cholesterol efflux in ECs and regulatory mechanisms. We found mature HDL particles were reduced in patients with coronary artery disease (CAD), which was associated with an increase in CC-chemokine ligand 2 (CCL2). In cultured primary human coronary artery endothelial cells and human umbilical vein endothelial cells, we determined that CCL2 suppressed the binding (4 °C) and association (37 °C) of HDL to/with ECs and HDL cellular internalization. Furthermore, CCL2 inhibited [(3)H]cholesterol efflux to HDL/apoA1 in ECs. We further found that CCL2 induced CC-chemokine receptor 2 (CCR2) expression and siRNA-CCR2 reversed CCL2 suppression on HDL binding, association, internalization, and on cholesterol efflux in ECs. Moreover, CCL2 induced p42/44 mitogen-activated protein kinase (MAPK) phosphorylation via CCR2, and p42/44 MAPK inhibition reversed the suppression of CCL2 on HDL metabolism in ECs. Our study suggests that CCL2 was elevated in CAD patients. CCL2 suppressed HDL internalization and cholesterol efflux via CCR2 induction and p42/44 MAPK activation in ECs. CCL2 induction may contribute to impair HDL function and form atherosclerosis in CAD. |
| Databáze: | OpenAIRE |
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