In-Vitro Carboxymethylation of Low Density Lipoprotein Alters its Metabolism Via the High-Affinity Receptor

Ke, Gempel; Kd, Gerbitz; Olgemöller, Bernhard; Ed, Schleicher

doi:10.1055/s-2007-1002089

Cited by 15 publications

(8 citation statements)

References 15 publications

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“…33,34 It is relevant that methylation of LDL abolished its recognition by LDL receptors, 35 retarded the degradation of aggregated LDL by macrophages, 36 and decreased CE formation in macrophages. 37 It is possible that hyperhomocysteinemia may inhibit lipid or protein methylation in LDL, which may result in increased endocytosis of LDL-derived CE in the lesions.…”

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia accelerates atherosclerosis in cystathionine β-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation

Wang

Jiang

Yang

et al. 2003

Blood

178

155

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Although hyperhomocysteinemia is an independent risk factor for cardiovascular disease, a direct role for homocysteine (Hcy) in this disease remains to be shown. Whereas diet-induced hyperhomocysteinemia promotes atherosclerosis in animal models, the effects of Hcy on atherogenesis in the absence of dietary perturbations is not known. We have generated double knock-out mice with targeted deletions of the genes for apolipoprotein E (apoE) and cystathionine ␤-synthase (CBS), which converts Hcy to cystathionine. ApoE ؊/؊ /CBS ؊/؊ mice developed aortic lesions even in the absence of dietary manipulation; lesion area and lesion cholesteryl ester (CE) and triglyceride (TG) contents increased with animal age and plasma Hcy levels. Plasma total cholesterol was significantly increased, whereas high density lipoprotein (HDL) cholesterol and TG concentrations of apoE ؊/؊ /CBS ؊/؊ mice were decreased. Cholesterol esterification and activities of enzymes catalyzing CE or TG formation in the vessel wall and in peritoneal macrophages were not changed by hyperhomocysteinemia. However, uptake of human acetyl-LDL, but not native low density lipoprotein (LDL), by mouse peritoneal macrophages was higher in the presence of hyperhomocysteinemia. These results suggest that isolated hyperhomocysteinemia is atherogenic and alters hepatic and macrophage lipoprotein metabolism, in part, by enhancing uptake of modified LDL. (Blood. 2003;101: 3901-3907)

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Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia accelerates atherosclerosis in cystathionine β-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation

Wang

Jiang

Yang

et al. 2003

Blood

178

155

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“…Further studies are needed to clarify the epitope structure of this antibody. Because CML does not undergo receptor recognition (56), it seems likely that non-CML structure(s) generated in GA-BSA may serve as a signal for the receptor recognition. Aldoamine, an Amadorirearranged GA adduct, has been shown to form Schiff base linkages with another amino group, leading to covalent cross-linking of proteins (17,18).…”

Section: Discussionmentioning

confidence: 99%

Glycolaldehyde, a reactive intermediate for advanced glycation end products, plays an important role in the generation of an active ligand for the macrophage scavenger receptor.

Nagai

Matsumoto²,

Xia³

et al. 2000

Diabetes

170

140

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. The negative charge of these ligands increased to a similar extent. However, GA-BSA, but not MG-BSA or GO-BSA, underwent receptor-mediated endocytosis by the macrophage-derived cell line RAW 264.7, which was effectively inhibited by glucose-derived AGE-BSA, acetylated LDL, and oxidized LDL, which are wellknown ligands for the macrophage type I and type II class A scavenger receptors (MSR-A). The endocytic uptake of GA-BSA by mouse peritoneal macrophages was also significant, but that by peritoneal macrophages from MSR-A-deficient mice was markedly reduced. Our results suggest that GA serves as an important intermediate for the generation of AGE structure(s) responsible for recognition by MSR-A.

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“…63 Glycated LDL reduces nitric oxide (NO) production and suppresses uptake and clearance of LDL through its receptor on endothelial cells. [63][64][65] …”

Section: Age Effects On Extracellular Functionmentioning

confidence: 99%

Advanced Glycation End Products

et al. 2006

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Abstract-Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars.AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis. The presence and accumulation of AGEs in many different cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes upregulation of the transcription factor nuclear factor-B and its target genes. Soluble AGEs activate monocytes, and AGEs in the basement membrane inhibit monocyte migration. AGE-bound RAGE increases endothelial permeability to macromolecules. AGEs block nitric oxide activity in the endothelium and cause the production of reactive oxygen species.

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In-Vitro Carboxymethylation of Low Density Lipoprotein Alters its Metabolism Via the High-Affinity Receptor

Cited by 15 publications

References 15 publications

Hyperhomocysteinemia accelerates atherosclerosis in cystathionine β-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation

Hyperhomocysteinemia accelerates atherosclerosis in cystathionine β-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation

Glycolaldehyde, a reactive intermediate for advanced glycation end products, plays an important role in the generation of an active ligand for the macrophage scavenger receptor.

Advanced Glycation End Products

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