Glycation as an atherogenic modification of LDL

Younis, Naveed; Sharma, Reena; Soran, Handrean; Charlton-Menys, Valentine; Elseweidy, Mohamed M.; Durrington, Paul N.

doi:10.1097/mol.0b013e328306a057

Cited by 86 publications

(66 citation statements)

References 80 publications

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“…LAL lysosomal acid lipase, SMC smooth muscle cells, TO TO901317, LXR agonist, RSG rosiglitasone, PPAR-gamma agonist. **P \ 0.01 molecules and scavenger receptors [1,16,26]. Our data extend these findings, revealing another effect of gLDL, namely the down regulation of LAL expression in SMC.…”

Section: Discussionsupporting

confidence: 81%

Modified Low Density Lipoproteins Decrease the Activity and Expression of Lysosomal Acid Lipase in Human Endothelial and Smooth Muscle Cells

Heltianu¹,

Robciuc²,

Botez³

et al. 2011

Cell Biochem Biophys

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Lysosomal acid lipase (LAL), the only lysosomal enzyme involved in the hydrolysis of LDL-cholesteryl esters, is a key regulator of cellular cholesterol and fatty acid homeostasis and its deficiency contributes to the pathophysiology of various diseases. In this study, we questioned whether oxidized or glycated LDL, a common occurrence in atherosclerosis and diabetes, affect the activity and expression of LAL in vascular endothelial cells (EC) and smooth muscle cells (SMC). LAL activity and expression were assayed in cultured human EC and SMC exposed to oxidized LDL (oxLDL), (±)9-hydroxyoctadecadienoic acid-cholesteryl ester (HODE), glycated LDL (gLDL), or native LDL (nLDL) as control, in the presence or absence of LXR or PPAR-gamma agonists. We found that LAL activity and expression were significantly down regulated by oxLDL and HODE in EC, and by gLDL in SMC. The LXR agonist T0901317 reversed the decreased LAL expression in modified LDL- or HODE-exposed EC (P < 0.001) and in gLDL-exposed SMC, whereas PPAR-gamma agonist rosiglitazone induced a low effect only in EC. In conclusion, modified LDL down regulates LAL expression in human EC and SMC by a process involving the LXR signaling pathway. This is the first demonstration that modified LDL modulate LAL expression, in a cell specific manner.

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Section: Discussionsupporting

confidence: 81%

Modified Low Density Lipoproteins Decrease the Activity and Expression of Lysosomal Acid Lipase in Human Endothelial and Smooth Muscle Cells

Heltianu¹,

Robciuc²,

Botez³

et al. 2011

Cell Biochem Biophys

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“…43 Furthermore, in patients with DM and dyslipidemia, glycation of apoprotein A attenuates the atheroprotective function of highdensity lipoprotein, and, in contrast, glycation of apoprotein B reinforces the low-density lipoprotein-induced inflammatory response. 44, 45 Thus, diabetic pathophysiology promotes an antiangiogenic process and meanwhile mitigates pro-angiogenic …”

Section: Discussionmentioning

confidence: 99%

Increased Serum Level of Soluble Vascular Endothelial Growth Factor Receptor-1 Is Associated With Poor Coronary Collateralization in Patients With Stable Coronary Artery Disease

Sun

Shen

Lü

et al. 2014

Circ J

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“…The relative resistance of LDL to glycation in vitro, indicated by the requirement for its exposure to supraphysiological concentrations of glucose for longer than its physiological circulating half-life, has been consistently reported. 33,[55][56][57] In a recent review, 10 earlier investigators reported employing glucose in the range 25-500 mmol/L for periods of up to 28 days and in the presence of elemental oxygen. The implication is that glycation occurs more readily in vivo.…”

Section: Discussionmentioning

confidence: 99%

High-density lipoprotein impedes glycation of low-density lipoprotein

Younis

Soran

Charlton-Menys

et al. 2012

Diabetes and Vascular Disease Research

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Glycation of low-density lipoprotein (LDL) increases its atherogenicity, but whether high-density lipoprotein (HDL) can protect LDL against glycation is not known. LDL and HDL were isolated from 32 volunteers with serum HDL cholesterol concentrations ranging from 0.76 to 2.01 (mean = 1.36) mmol/L. Glycation of LDL was induced by incubation with 0-80 mmol/L glucose for 7 days at 37°C under nitrogen in the presence of and absence of human HDL. Glycation of LDL apolipoprotein B (apoB) doubled at glucose 50 and 80 mmol/L (both p < 0.001), and this increase was ameliorated by HDL. In the absence of glucose, 0.11 (0.01) [mean (standard error, SE)] mg apoB/mg LDL protein was glycated increasing to 0.22 (0.02) mg/mg at glucose 80 mmol/L in the absence of HDL, but remaining at 0.13 (0.01) mg/mg when autologous HDL was present. Heterologous HDL from a further study of 12 healthy participants was similarly effective in impeding LDL apoB glycation. HDL impeded not only glycation but also the lipid peroxidation, free amino group consumption and increased electrophoretic mobility of LDL which accompanied glycation. HDL from participants with higher serum paraoxonase1 (PON1) was more effective in impeding glycation and the related processes. In conclusion, HDL can impede the glucose-induced glycoxidation of LDL. PON1 may be important for this function of HDL.

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Glycation as an atherogenic modification of LDL

Cited by 86 publications

References 80 publications

Modified Low Density Lipoproteins Decrease the Activity and Expression of Lysosomal Acid Lipase in Human Endothelial and Smooth Muscle Cells

Modified Low Density Lipoproteins Decrease the Activity and Expression of Lysosomal Acid Lipase in Human Endothelial and Smooth Muscle Cells

Increased Serum Level of Soluble Vascular Endothelial Growth Factor Receptor-1 Is Associated With Poor Coronary Collateralization in Patients With Stable Coronary Artery Disease

High-density lipoprotein impedes glycation of low-density lipoprotein

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