Oxidation-induced loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on vasorelaxation

Abstract

Several current diseases are associated with an increase in the oxidation of HDL, which is likely to impair their functionality. Our aim was to identify whether oxidation could change the protective effect of HDL against the deleterious effect on vasoreactivity induced by oxidative stress. HDL from healthy subjects were oxidized in vitro by Cu(2+), and the ability of oxidized HDL to counteract the inhibitory effect of oxidized LDL on acetylcholine-induced vasodilation was tested on isolated rabbit aorta rings. Oxidation of HDL was evidenced by the increase in the 7-oxysterols/cholesterol ratio (3.20 ± 1.12 vs 0.02 ± 0.01 % in native HDL, p < 0.05). Oxidized LDL inhibited endothelium-dependent vasodilation (E max = 50.2 ± 5.0 vs 92.5 ± 1.7 % for incubation in Kreb's buffer, p < 0.05) and native HDL counteracted this inhibition (E max = 72.4 ± 4.8 vs 50.2 ± 5.0 % p < 0.05). At the opposite, oxidized HDL had no effect on oxidized LDL-induced inhibition on endothelium-dependent vasorelaxation (E max = 53.7 ± 4.8 vs 50.2 ± 5.0 %, NS). HDL oxidation is associated with a decreased ability of HDL to remove 7-oxysterols from oxidized LDL. In conclusion, these results show that oxidation of HDL induces the loss of their protective effect against endothelial dysfunction, which could promote atherosclerosis in diseases associated with increased oxidative stress.

Small dense HDLs display potent vasorelaxing activity, reflecting their elevated content of sphingosine-1-phosphate

“…Indeed, in vitro oxidation of HDL from healthy subjects resulted in the loss of HDLS1P with a concomitant reduction in HDL capacity to uptake S1P in vitro (15). Consistent with this observation, oxidation of HDL from healthy subjects re duced its ability to counteract the inhibitory effect of ox LDL on endotheliumdependent vasorelaxation (40).…”

“…The maximal relaxation (E max ) evoked by acetylcholine and ex pressed as a percentage of the contraction to arterenol hydrochloride (0.3 mol/l) was calculated from experimental data. To reduce variation among experiments resulting from different intrinsic properties of aortic vessels, three different aortic rings were used and the average results were reported (40).…”

The influence of renal function on the association of rs854560 polymorphism of paraoxonase 1 gene with long-term prognosis in patients after myocardial infarction

“…This phenomenon may be explained by decreased PON1 activity in the AA homozygotes of rs854560 SNP [ 7 ]. This results in the diminished antioxidant activity of HDL cholesterol, an increase in oxidative stress and endothelial dysfunction [ 6 , 17 ], including decreased NO production [ 6 ].…”

The role of high density lipoprotein in the determination of the vascular effects of chronic exercise training in hypertensive patients

“…Oxidized low-density lipoprotein (oxLDL) has been reported to cause depletion of caveolae from eNOS accompanied by attenuation of the acetylcholine-induced activation of eNOS, while HDL has been shown to reverse the oxLDL-induced impairment of endothelium-dependent vasorelaxation. 9 However, oxHDL has been demonstrated to have no effect on the oxLDL-induced inhibition of endothelium-dependent vasorelaxation, implying that the vasorelaxant properties of HDL can be attributed the non-oxidized form of HDL. 9 With regard to the influence of exercise on the HDL-induced vasodilation, Chen et al reported an augmentation of the suppressive effect of HDL on the oxLDL-induced inhibition of endothelium-dependent vasodilation in thoracic aortas isolated from rats subjected to aerobic exercise training for eight weeks compared with aortas from sedentary rats.…”

“…9 However, oxHDL has been demonstrated to have no effect on the oxLDL-induced inhibition of endothelium-dependent vasorelaxation, implying that the vasorelaxant properties of HDL can be attributed the non-oxidized form of HDL. 9 With regard to the influence of exercise on the HDL-induced vasodilation, Chen et al reported an augmentation of the suppressive effect of HDL on the oxLDL-induced inhibition of endothelium-dependent vasodilation in thoracic aortas isolated from rats subjected to aerobic exercise training for eight weeks compared with aortas from sedentary rats. 10 In this study, the effects of chronic exercise and HDL on the amelioration of vascular function, through the attenuation of oxLDL-induced inhibition of endotheliumdependent vasodilation, were reported to be independent and additive.…”