High-density lipoprotein impedes glycation of low-density lipoprotein

Abstract

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.

Antioxidant properties of HDL

“…We have also shown that HDL can impede the modification of LDL by glycation in vitro , and that this anti-glycative function of HDL is more marked with HDL obtained from people with higher serum PON1 activity (Younis et al, 2013 ). We noted in these experiments that LDL is relatively resistant to glycation in the absence of oxygen, such that supraphysiological glucose concentrations are required.…”

“…We have contributed to the notion that paraoxonase 1 (PON1), an enzyme located almost exclusively on HDL, is important in impeding oxidative modification of LDL (Mackness et al, 1991 , 1993 ; Durrington et al, 2001 ). Our recent work has focused on glycation as an atherogenic modification of LDL and this too has led us back to PON1 (Younis et al, 2013 ). Other HDL components have also been conjectured to be involved in preventing atherogenic LDL modification and evidence increasingly points to a coordination of these with PON1.…”

Paraoxonase 1 activities, regulation, and interactions with atherosclerotic lesion

“…HDL-PON1 was shown recently to impede LDL glycation and lipoprotein peroxidation. The enzyme protecting effect augmented with increased PON1 content [8].…”

In Vitro and In Silico Studies on the Toxic Effects of Antibacterial Drugs as Human Serum Paraoxonase 1 Inhibitor

“…These tasks include to protect lipoproteins and cells against oxidative stress and also to inhibit atherogenesis and lipoprotein peroxidation . This protective effects of PON1 are associated with the enzyme level in the serum . Recent studies found that PON1 levels have low in patients with atherosclerosis, diabetes, and hypercholesterolemia and overexpression of PON1 especially impedes the development of cardiovascular diseases.…”