Implication of N�-Carboxymethyllysine in altered metabolism of low density lipoproteins from patients with type 2 diabetes and cardiovascular diseases

Khaled Abdul-Aziz Ahmed, . and Sekaran Muniandy, . and Ikram Shah Ismail, . (2008) Implication of N�-Carboxymethyllysine in altered metabolism of low density lipoproteins from patients with type 2 diabetes and cardiovascular diseases. [Proceedings Paper]

Low-density lipoproteins LDL the major cholesterol carriers of human plasma contain a single copy of apolipoprotein B apoB. ApoB a ligand for the cell surface LDL receptor has an important role in cholesterol metabolism. Biochemical modification of apoB such as modification with advanced glycation end-products AGEs or glycoxidation can dramatically affect the functional integrity of LDL and subsequently impair capacity to be taken up by cell surface LDL receptors. Alternatively AGE-LDL present in blood circulation due to hyperglycemia can result in increased LDL uptake by macrophages and therefore the increased atherogenic potential of LDL. Diabetic patients have elevated concentrations of AGE-modified LDL AGELDL. NE-Carboxymethyllysine CML the glycoxidation product is the predominant AGE found in vivo. The purpose of this study was to clarify the role of the glycoxidation product NE-Carboxymethyllysine on the metabolism of low-density lipoprotein LDL and give rise to increased risks of cardiovascular diseases in Type 2 diabetic patients. In this study LDL from diabetic patients and healthy controls were isolated labeled with the fluorescence dye 3 3;-dioctadecyloxa-carbocyanine perchlorate DiI and subjected to modification including oxidation glycation glycoxidation and carbomethylation. The susceptibility of LDL to in vitro oxidation was assessed. Receptor-mediated binding and uptake of fluorescently labeled native oxidized- AGE- glycoxidized-and CML-LDL were studied in HepG2 cells. LDL from diabetic patients and AGE-LDL were more susceptible to copper-mediated oxidation than LDL from controls. The receptor-mediated uptake of fluorescently labeled LDL from Type 2 diabetes with cardiovascular diseases glycoxidized-LDL and CML-LDL was significantly lower than that for LDL from both diabetics without CVD and healthy control subjects in HepG2 cells. From these results we conclude that glycoxidation and carbomethylation of LDL may be largely responsible for the defective uptake of LDL by the LDL receptor rather than AGE-LDL alone and these findings confirm the previous studies that CML is the major glycoxidation product present in vivo. CML may be considered as a marker of interest for early detection of Type 2 diabetic complications and may represent a target for the glycaemic control in those patients.

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Abstract

Low-density lipoproteins LDL the major cholesterol carriers of human plasma contain a single copy of apolipoprotein B apoB. ApoB a ligand for the cell surface LDL receptor has an important role in cholesterol metabolism. Biochemical modification of apoB such as modification with advanced glycation end-products AGEs or glycoxidation can dramatically affect the functional integrity of LDL and subsequently impair capacity to be taken up by cell surface LDL receptors. Alternatively AGE-LDL present in blood circulation due to hyperglycemia can result in increased LDL uptake by macrophages and therefore the increased atherogenic potential of LDL. Diabetic patients have elevated concentrations of AGE-modified LDL AGELDL. NE-Carboxymethyllysine CML the glycoxidation product is the predominant AGE found in vivo. The purpose of this study was to clarify the role of the glycoxidation product NE-Carboxymethyllysine on the metabolism of low-density lipoprotein LDL and give rise to increased risks of cardiovascular diseases in Type 2 diabetic patients. In this study LDL from diabetic patients and healthy controls were isolated labeled with the fluorescence dye 3 3;-dioctadecyloxa-carbocyanine perchlorate DiI and subjected to modification including oxidation glycation glycoxidation and carbomethylation. The susceptibility of LDL to in vitro oxidation was assessed. Receptor-mediated binding and uptake of fluorescently labeled native oxidized- AGE- glycoxidized-and CML-LDL were studied in HepG2 cells. LDL from diabetic patients and AGE-LDL were more susceptible to copper-mediated oxidation than LDL from controls. The receptor-mediated uptake of fluorescently labeled LDL from Type 2 diabetes with cardiovascular diseases glycoxidized-LDL and CML-LDL was significantly lower than that for LDL from both diabetics without CVD and healthy control subjects in HepG2 cells. From these results we conclude that glycoxidation and carbomethylation of LDL may be largely responsible for the defective uptake of LDL by the LDL receptor rather than AGE-LDL alone and these findings confirm the previous studies that CML is the major glycoxidation product present in vivo. CML may be considered as a marker of interest for early detection of Type 2 diabetic complications and may represent a target for the glycaemic control in those patients.

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Item Type:	Proceedings Paper
Additional Information:	Available at Perpustakaan Sultan Abdul Samad Uni-versiti Putra Malaysia 43400 UPM Serdang Selangor Malaysia. mal RM666 H33 B573 Call Number
AGROVOC Term:	Lipoproteins
AGROVOC Term:	Diabetes mellitus
AGROVOC Term:	Cardiovascular diseases
AGROVOC Term:	Cholesterol
AGROVOC Term:	Isolation
AGROVOC Term:	Risk factors
AGROVOC Term:	Lipid peroxidation
AGROVOC Term:	Blood circulation
AGROVOC Term:	In vitro
AGROVOC Term:	ELISA
Geographical Term:	MALAYSIA
Depositing User:	Ms. Suzila Mohamad Kasim
Last Modified:	24 Apr 2025 05:15
URI:	http://webagris.upm.edu.my/id/eprint/12861

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