N(epsilon)-(Carboxymethyl)lysine and Coronary Atherosclerosis-Associated Low Density Lipoprotein Abnormalities in Type 2 Diabetes: Current Status

Overview

Journal J Clin Biochem Nutr

Specialty Biochemistry

Date 2009 Jan 30

PMID 19177184

Citations 11

Authors

Khaled A Ahmed

Sekaran Muniandy

Ikram S Ismail

Affiliations

Soon will be listed here.

Abstract

In comparison to the general population, individuals with diabetes suffer a 3- to 4-fold increased risk for developing complications of atherosclerosis and vascular insufficiency. This fact should be taken into account to develop a suitable determinant for the early detection of these complications and subsequently reduce the adverse effect of type 2 diabetes. In vitro experiments have shown that the products of glucose auto-oxidation and Amadori adducts are both potential sources of N(epsilon)-(carboxymethyl)lysine (CML). Excessive formation of CML on low density lipoprotein (LDL) has been proposed to be an important mechanism for the dyslipidemia and accelerated atherogenesis observed in patients with type 2 diabetes. It has been postulated that the uptake of CML-LDL by LDL receptors is impaired, thereby decreasing its clearance from the blood circulation. Alternatively, the uptake of these modified LDL particles by scavenger receptors on macrophages and vascular smooth muscle cells (SMCs) and by AGE receptors on endothelial cells, SMCs, and monocytes is highly enhanced and this, in turn, is centrally positioned to contribute to the pathogenesis of diabetic vascular complications especially coronary artery disease. The present review summarizes the up-to-date information on effects and mechanism of type 2 diabetes-associated coronary atherosclerosis induced by CML-LDL modification.

Citing Articles

Nε-(1-Carboxymethyl)-L-lysine/RAGE Signaling Drives Metastasis and Cancer Stemness through ERK/NFκB axis in Osteosarcoma.

Chang T, Lan K, Wu C, Sheu M, Yang R, Liu S Int J Biol Sci. 2024; 20(3):880-896.

PMID: 38250151 PMC: 10797696. DOI: 10.7150/ijbs.90817.

Comparative analysis of Nε-carboxymethyl-lysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients.

Shrivastav D, Singh D, Mir R, Mehra P, Mehta V, Dabla P World J Diabetes. 2024; 14(12):1754-1765.

PMID: 38222780 PMC: 10784802. DOI: 10.4239/wjd.v14.i12.1754.

Metabolomic Analysis of Skeletal Muscle in Aged Mice.

Uchitomi R, Hatazawa Y, Senoo N, Yoshioka K, Fujita M, Shimizu T Sci Rep. 2019; 9(1):10425.

PMID: 31320689 PMC: 6639307. DOI: 10.1038/s41598-019-46929-8.

Comparative Analysis of AGE and RAGE Levels in Human Somatic and Embryonic Stem Cells under HO-Induced Noncytotoxic Oxidative Stress Conditions.

Barandalla M, Haucke E, Fischer B, Navarrete Santos A, Colleoni S, Galli C Oxid Med Cell Longev. 2017; 2017:4240136.

PMID: 29104727 PMC: 5623800. DOI: 10.1155/2017/4240136.

Anti-atherosclerotic effect of traditional fermented cheese whey in atherosclerotic rabbits and identification of probiotics.

Nabi X, Ma C, Manaer T, Heizati M, Wulazibieke B, Aierken L BMC Complement Altern Med. 2016; 16:309.

PMID: 27553960 PMC: 4995647. DOI: 10.1186/s12906-016-1285-8.

References

Huxley R, Barzi F, Woodward M . Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2005; 332(7533):73-8. PMC: 1326926. DOI: 10.1136/bmj.38678.389583.7C. View

Kapinsky M, Torzewski M, Buchler C, Duong C, Rothe G, Schmitz G . Enzymatically degraded LDL preferentially binds to CD14(high) CD16(+) monocytes and induces foam cell formation mediated only in part by the class B scavenger-receptor CD36. Arterioscler Thromb Vasc Biol. 2001; 21(6):1004-10. DOI: 10.1161/01.atv.21.6.1004. View

Singh R, Barden A, Mori T, Beilin L . Advanced glycation end-products: a review. Diabetologia. 2001; 44(2):129-46. DOI: 10.1007/s001250051591. View

Cariou B, Bonnevie L, Mayaudon H, Dupuy O, Ceccaldi B, Bauduceau B . Angiographic characteristics of coronary artery disease in diabetic patients compared with matched non-diabetic subjects. Diabetes Nutr Metab. 2000; 13(3):134-41. View

Wang X, Greilberger J, Ratschek M, Jurgens G . Oxidative modifications of LDL increase its binding to extracellular matrix from human aortic intima: influence of lesion development, lipoprotein lipase and calcium. J Pathol. 2001; 195(2):244-50. DOI: 10.1002/path.935. View

Schmidt A, STERN D . RAGE: a new target for the prevention and treatment of the vascular and inflammatory complications of diabetes. Trends Endocrinol Metab. 2000; 11(9):368-75. DOI: 10.1016/s1043-2760(00)00311-8. View

Airaksinen K, Salmela P, Linnaluoto M, Ikaheimo M, Ahola K, Ryhanen L . Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen. Cardiovasc Res. 1993; 27(6):942-5. DOI: 10.1093/cvr/27.6.942. View

Tsai E, Hirsch I, Brunzell J, Chait A . Reduced plasma peroxyl radical trapping capacity and increased susceptibility of LDL to oxidation in poorly controlled IDDM. Diabetes. 1994; 43(8):1010-4. DOI: 10.2337/diab.43.8.1010. View

Linton M, Fazio S . Class A scavenger receptors, macrophages, and atherosclerosis. Curr Opin Lipidol. 2001; 12(5):489-95. DOI: 10.1097/00041433-200110000-00003. View

10.

Mykkanen L, Kuusisto J, Pyorala K, Laakso M . Cardiovascular disease risk factors as predictors of type 2 (non-insulin-dependent) diabetes mellitus in elderly subjects. Diabetologia. 1993; 36(6):553-9. DOI: 10.1007/BF02743273. View

11.

Griffin E, Re A, Hamel N, Fu C, Bush H, McCaffrey T . A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation. Nat Med. 2001; 7(7):840-6. DOI: 10.1038/89969. View

12.

. Economic consequences of diabetes mellitus in the U.S. in 1997. American Diabetes Association. Diabetes Care. 1998; 21(2):296-309. DOI: 10.2337/diacare.21.2.296. View

13.

Schalkwijk C, Baidoshvili A, Stehouwer C, van Hinsbergh V, Niessen H . Increased accumulation of the glycoxidation product Nepsilon-(carboxymethyl)lysine in hearts of diabetic patients: generation and characterisation of a monoclonal anti-CML antibody. Biochim Biophys Acta. 2004; 1636(2-3):82-9. DOI: 10.1016/j.bbalip.2003.07.002. View

14.

Schleicher E, Wagner E, Nerlich A . Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest. 1997; 99(3):457-68. PMC: 507819. DOI: 10.1172/JCI119180. View

15.

Fu M, Requena J, Jenkins A, Lyons T, Baynes J, Thorpe S . The advanced glycation end product, Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. J Biol Chem. 1996; 271(17):9982-6. DOI: 10.1074/jbc.271.17.9982. View

16.

Sakata N, Uesugi N, Takebayashi S, Nagai R, Jono T, Horiuchi S . Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis. Cardiovasc Res. 2001; 49(2):466-75. DOI: 10.1016/s0008-6363(00)00262-5. View

17.

Hammoud T, Tanguay J, Bourassa M . Management of coronary artery disease: therapeutic options in patients with diabetes. J Am Coll Cardiol. 2000; 36(2):355-65. DOI: 10.1016/s0735-1097(00)00732-4. View

18.

Price D, Rhett P, Thorpe S, Baynes J . Chelating activity of advanced glycation end-product inhibitors. J Biol Chem. 2001; 276(52):48967-72. DOI: 10.1074/jbc.M108196200. View

19.

Klein R, WOHLTMANN H, Lopes-Virella M . Influence of glycemic control on interaction of very-low- and low-density lipoproteins isolated from type I diabetic patients with human monocyte-derived macrophages. Diabetes. 1992; 41(10):1301-7. DOI: 10.2337/diab.41.10.1301. View

20.

Portero-Otin M, Pamplona R, Bellmunt M, Bergua M, Prat J . Glycaemic control and in vivo non-oxidative Maillard reaction: urinary excretion of pyrraline in diabetes patients. Eur J Clin Invest. 1997; 27(9):767-73. DOI: 10.1046/j.1365-2362.1997.1900740.x. View