Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase

Mackness, Michael I.; Arrol, Sharon; Abbott, Caroline A.; Durrington, Paul N.

doi:10.1016/0021-9150(93)90183-u

Cited by 737 publications

(473 citation statements)

References 20 publications

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“…HDL inhibit the LDL oxidation process by removing lipid peroxides and oxidised derivatives of cholesterol from LDL via cholesteryl ester transfer protein [18]. The two HDL-associated enzymes, PON and platelet-activated factor-acetyl hydrolase (PAF-AH) hydrolyse oxidised cholesterol or hydroperoxides [19][20][21]. Furthermore, HDL prevent the depletion in free cholesterol of endothelial cell caveolae induced by ox-LDL, thus allowing eNOS to stay in caveolae, where it can be activated by vasodilatory ligands of G protein-coupled receptors [22].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…In the past few decades, it has become evident that high density lipoprotein (HDL) has antioxidant properties that protect LDL and HDL particles from oxidation. During this process, the HDLassociated enzyme paraoxonase1 (PON1) has been suggested as a possible mechanistic cause of this phenomenon [3,28,29,33,49]. PON1 belongs to the paraoxonase (PON) gene family which is located on chromosome 7q21.3-22.1 [37].…”

Section: Introductionmentioning

confidence: 99%

“…PON1 has protective action against atherosclerosis in both in vitro and in vivo models. Indeed, PON1 protects LDL particles against copper-induced lipid oxidation in vitro [3,28,29] and transgenic mice overexpressing the human PON1 gene have reduced atherosclerotic lesions [48]. Moreover, PON1 knockout mice display accelerated atherosclerosis progression and increased lipid oxidation [40,42,43].…”

Section: Introductionmentioning

confidence: 99%

Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status

Nagila

Permpongpaiboon

Tantrarongroj

et al. 2009

Pharmacological Reports

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Abstract:It has been proposed that paraoxonase1 (PON1), a high density lipoprotein (HDL)-associated esterase/lactonase, has antiatherosclerotic properties. The activity of PON1 is influenced by PON1 polymorphisms. However, the influence of PON1 polymorphisms on PON1 activity and oxidative stress in response to lipid-lowering drugs remains poorly understood. The objective of the present study was to investigate the effects of atorvastatin on PON1 activity and oxidative status. The influence of PON1 polymorphisms on PON1 activity and oxidative status in response to atorvastatin treatment was also evaluated. In total, 22 hypercholesterolemic patients were treated with atorvastatin at a dose of 10 mg/day for 3 months. Lipid profile, lipid oxidation markers (malondialdehyde (MDA), conjugated diene (CD), total peroxides (TP)), total antioxidant substance (TAS), oxidative stress index (OSI), and paraoxonase1 activity were determined before and after treatment. L55M, Q192R, and T(-107)C PON1 polymorphisms were also determined. Atorvastatin treatment significantly reduced the levels of total cholesterol (24.5%), low density lipoprotein (LDL) cholesterol (25.4%), triglycerides (24.4%), CD (4.4%), MDA (15.2%), TP (13.0%) and OSI (24.0%), and significantly increased the levels of TAS (27.3%), and PON1 activity (14.0%). Interestingly, the increase in PON1 activity and the reduction in oxidative stress in response to atorvastatin were influenced only by the PON1 T-107C polymorphism. Atorvastatin treatment improved the lipid profile, lipid oxidation, and oxidative/antioxidative status markers including the activity of PON1 towards paraoxon. These beneficial effects may be attributed to the antioxidant properties of statins and the increase in PON1 activity. The increase in PON1 activity was enhanced by the PON1 T-107C polymorphism.

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“…It is noted that PON1 associates with high-density lipoprotein (HDL) [1] and inhibits the oxidation of low-density lipoprotein (LDL) and HDL [2,3]. PON1 knockout mice were unable to protect against the progression of atherosclerosis by feeding on a high fat and high cholesterol diet [4], and atherosclerotic lesion formation was decreased in PON1 transgenic mice [5].…”

Section: Introductionmentioning

confidence: 99%

Pitavastatin induces PON1 expression through p44/42 mitogen-activated protein kinase signaling cascade in Huh7 cells

et al. 2009

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Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase

Cited by 737 publications

References 20 publications

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

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

Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status

Pitavastatin induces PON1 expression through p44/42 mitogen-activated protein kinase signaling cascade in Huh7 cells

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