Isoda, KikuoFolco, EduardoMarwali, M. RezaOhsuzu, FumitakaLibby, Peter2017-04-272008Isoda, 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.2007.10.035.0021-9150http://nrs.harvard.edu/urn-3:HUL.InstRepos:32605690Background 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). Conclusions 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.en-USDiabetes mellitusCholesterolLipoproteinMetabolismAtherosclerosisJournal Article2017-04-2710.1016/j.atherosclerosis.2007.10.035