Glycated LDL increases monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1-mediated chemotaxis.
BACKGROUND
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.


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 (48h) (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.
Isoda
Kikuo
K
Donald W. Reynolds Cardiovascular Clinical Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Folco
Eduardo
E
Marwali
M Reza
MR
Ohsuzu
Fumitaka
F
Libby
Peter
P
D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D000093844:Glycated Proteins
D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D054390:Receptors, CCR2; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins