Glycated LDL Increases Monocyte CC Chemokine Receptor 2 Expression and Monocyte Chemoattractant Protein-1-mediated Chemotaxis

Overview

Journal Atherosclerosis

Publisher Elsevier

Specialty Cardiology & Vascular Diseases

Date 2008 Jan 1

PMID 18164016

Citations 18

Authors

Kikuo Isoda

Eduardo Folco

M Reza Marwali

Fumitaka Ohsuzu

Peter Libby

Affiliations

Soon will be listed here.

Abstract

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.

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 (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.

Citing Articles

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References

Cho H, Choi S, Hwang K, Oh S, Kim H, Yoon D . The Src/PLC/PKC/MEK/ERK signaling pathway is involved in aortic smooth muscle cell proliferation induced by glycated LDL. Mol Cells. 2005; 19(1):60-6. View

Virmani R, Burke A, Kolodgie F . Morphological characteristics of coronary atherosclerosis in diabetes mellitus. Can J Cardiol. 2006; 22 Suppl B:81B-84B. PMC: 2780829. DOI: 10.1016/s0828-282x(06)70991-6. View

Itabe H, Ueda M . Measurement of plasma oxidized low-density lipoprotein and its clinical implications. J Atheroscler Thromb. 2007; 14(1):1-11. DOI: 10.5551/jat.14.1. View

Isoda K, Folco E, Shimizu K, Libby P . AGE-BSA decreases ABCG1 expression and reduces macrophage cholesterol efflux to HDL. Atherosclerosis. 2006; 192(2):298-304. DOI: 10.1016/j.atherosclerosis.2006.07.023. View

Velarde V, Jenkins A, Christopher J, Lyons T, Jaffa A . Activation of MAPK by modified low-density lipoproteins in vascular smooth muscle cells. J Appl Physiol (1985). 2001; 91(3):1412-20. DOI: 10.1152/jappl.2001.91.3.1412. View

Basta G, Lazzerini G, Massaro M, Simoncini T, Tanganelli P, Fu C . Advanced glycation end products activate endothelium through signal-transduction receptor RAGE: a mechanism for amplification of inflammatory responses. Circulation. 2002; 105(7):816-22. DOI: 10.1161/hc0702.104183. View

Libby P, Ridker P, Maseri A . Inflammation and atherosclerosis. Circulation. 2002; 105(9):1135-43. DOI: 10.1161/hc0902.104353. View

Napoli C, Lerman L, de Nigris F, Loscalzo J, Ignarro L . Glycoxidized low-density lipoprotein downregulates endothelial nitricoxide synthase in human coronary cells. J Am Coll Cardiol. 2002; 40(8):1515-22. DOI: 10.1016/s0735-1097(02)02306-9. View

Menten P, Wuyts A, Van Damme J . Macrophage inflammatory protein-1. Cytokine Growth Factor Rev. 2002; 13(6):455-81. DOI: 10.1016/s1359-6101(02)00045-x. View

10.

Libby P . Inflammation in atherosclerosis. Nature. 2002; 420(6917):868-74. DOI: 10.1038/nature01323. View

11.

Yamagishi S, Takeuchi M, Inagaki Y, Nakamura K, Imaizumi T . Role of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy. Int J Clin Pharmacol Res. 2004; 23(4):129-34. View

12.

Burke A, Kolodgie F, Zieske A, Fowler D, Weber D, Varghese P . Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. Arterioscler Thromb Vasc Biol. 2004; 24(7):1266-71. DOI: 10.1161/01.ATV.0000131783.74034.97. View

13.

Steinbrecher U, Witztum J . Glucosylation of low-density lipoproteins to an extent comparable to that seen in diabetes slows their catabolism. Diabetes. 1984; 33(2):130-4. DOI: 10.2337/diab.33.2.130. View

14.

Lorenzi M, Cagliero E, Markey B, Henriksen T, Witztum J, Sampietro T . Interaction of human endothelial cells with elevated glucose concentrations and native and glycosylated low density lipoproteins. Diabetologia. 1984; 26(3):218-22. DOI: 10.1007/BF00252411. View

15.

Jack C, Sheridan B, Kennedy L, Stout R . Non-enzymatic glycosylation of low-density lipoprotein. Results of an affinity chromatography method. Diabetologia. 1988; 31(2):126-7. DOI: 10.1007/BF00395561. View

16.

Steinberg D, Parthasarathy S, Carew T, Khoo J, Witztum J . Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989; 320(14):915-24. DOI: 10.1056/NEJM198904063201407. View

17.

Tames F, Mackness M, Arrol S, Laing I, Durrington P . Non-enzymatic glycation of apolipoprotein B in the sera of diabetic and non-diabetic subjects. Atherosclerosis. 1992; 93(3):237-44. DOI: 10.1016/0021-9150(92)90260-n. View

18.

Lyons T, Li W, Jokl R . Toxicity of mildly modified low-density lipoproteins to cultured retinal capillary endothelial cells and pericytes. Diabetes. 1994; 43(9):1090-5. DOI: 10.2337/diab.43.9.1090. View

19.

Howard B . Lipoprotein metabolism in diabetes. Curr Opin Lipidol. 1994; 5(3):216-20. DOI: 10.1097/00041433-199405030-00009. View

20.

Penn M, Chisolm G . Oxidized lipoproteins, altered cell function and atherosclerosis. Atherosclerosis. 1994; 108 Suppl:S21-9. DOI: 10.1016/0021-9150(94)90150-3. View