Glycated LDL increases monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated chemotaxis
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CitationIsoda, Kikuo, Eduardo Folco, M. Reza Marwali, Fumitaka Ohsuzu, and Peter Libby. 2008. “Glycated LDL Increases Monocyte CC Chemokine Receptor 2 Expression and Monocyte Chemoattractant Protein-1-Mediated Chemotaxis.” Atherosclerosis 198 (2) (June): 307–312. doi:10.1016/j.atherosclerosis.2007.10.035.
Previous reports have suggested that levels of advanced glycation end product-modified LDL (AGE-LDL) increase in patients with diabetes due to elevated plasma glucose. However, understanding of the mechanisms by which AGE-LDL may accelerate atherogenesis remains incomplete.
Methods and results
Microarray and reverse transcription real-time PCR (RT-PCR) analyses revealed that AGE-LDL significantly increased levels of CC chemokine receptor 2 (CCR2) mRNA in human macrophages compared with LDL, an effect accompanied by increased levels of CCR2 protein. Flow cytometry also showed that AGE-LDL increases CCR2 expression on the cell surface following stimulation (48 h) (P < 0.05). This effect appeared to depend on the receptor for AGE (RAGE), since an anti-RAGE antibody significantly blocked increased CCR2 mRNA. Functional studies demonstrated that exposure of THP-1 monocytoid cells to AGE-LDL increases chemotaxis mediated by monocyte chemoattractant protein-1 (MCP-1) up to 3-fold compared to LDL treatment (P < 0.05).
These data show that AGE-LDL can increase CCR2 expression in macrophages and stimulate the chemotactic response elicited by MCP-1. This novel mechanism may contribute to accelerated atherogenesis in diabetic patients.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32605690
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