Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation

Abstract

Aims/hypothesis: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by oxidised LDL. Subjects and methods: Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by oxidised LDL. Results: Oxidised LDL inhibited endothelium-dependent vasodilation (maximal relaxation [Emax]=58.2± 14.6 vs 99.3±5.2% for incubation without any lipoprotein, p<0.0001). HDL from control subjects significantly reduced the inhibitory effect of oxidised LDL on vasodilatation (Emax=77.6±12.9 vs 59.5±7.7%, p<0.001), whereas HDL from type 2 diabetic patients had no effect (Emax=52.4±20.4 vs 57.2±18.7%, NS). HDL triglyceride content was significantly higher in type 2 diabetic patients than in control subjects (5.3±2.2 vs 3.1±1.4%, p<0.01) and was highly inversely correlated to Emax for oxidised LDL+HDL in type 2 diabetic patients (r=−0.71, p<0.005). Conclusions/interpretation: In type 2 diabetes mellitus, the ability of HDL to counteract the inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL is impaired and is inversely correlated with HDL triglyceride content. These findings suggest that HDL are less atheroprotective in type 2 diabetic patients than in control subjects.

HDL particles from type 1 diabetic patients are unable to reverse the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation

“…Indeed, lipid peroxides and oxidised derivatives of cholesterol are transferred from LDL to HDL, where they can be hydrolysed by HDL-associated enzymes such as PON and platelet-associated-factor acetyl hydrolase. As far as NO production is concerned, HDL particles are capable of stimulating endothelial NO synthase, after binding to cell surface receptors such as scavenger receptor BI or the lysophospholipid receptor S1P 3 [6].…”

“…Biochemical measurements Glycaemia, HbA 1c , lipid parameters and PON were measured as previously described [6]. Apolipoprotein E and apolipoprotein CIII were measured using Immuno Chimie International reagents (Bouffémont, France) on a Dimension analyser (Dade Behring, Newark, DE, USA).…”

“…Preparation of lipoproteins The different lipoprotein subclasses were isolated from serum or plasma by sequential flotation ultracentrifugation, according to their density [6]. The oxidation of LDL was performed by incubating freshly prepared LDL from normolipidaemic donors as previously described [6].…”

“…The oxidation of LDL was performed by incubating freshly prepared LDL from normolipidaemic donors as previously described [6]. Vasoreactivity on rabbit aorta rings Vasoreactivity experiments were performed on rabbit (Charles River, L'Arbresle, France) aorta rings following a previously described protocol [6].…”

“…Due to these multiple modifications, HDL particles from type 1 diabetic patients may be less protective against impairments of vasorelaxation than HDL particles from healthy individuals [6]. In the present study we investigated this possibility using isolated aorta rings, a previously validated model.…”