Paraoxonase-1 arylesterase activity is an independent predictor of myeloperoxidase levels in overweight patients with or without cardiovascular complications

Zsíros, Noémi; Koncsos, Péter; Lőrincz, Hajnalka; Serés, I.; Katkó, Mónika; Szentpéteri, Anita; Varga, V.; Fülöp, Péter; Paragh, György; Harangi, Mariann

doi:10.1016/j.clinbiochem.2016.03.011

Cited by 14 publications

(15 citation statements)

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“…Our previous study on a similar patient population also highlighted the importance of this reciprocal inhibition [29] . Furthermore, a recent study showed that serum MPO/PON1 ratio may be a potential indicator of dysfunctional highdensity lipoprotein and risk stratification in coronary artery disease [30] .…”

Section: Discussionmentioning

confidence: 99%

HDL subfraction distribution and HDL function in untreated dyslipidemic patients

Harangi¹,

Szentpéteri²,

Nádró³

et al. 2017

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Aim:The protective role of high-density lipoprotein (HDL) against atherosclerosis is well known. However, both structural and functional changes of the HDL particles may affect its protective efficacy. Increased levels of HDL-associated myeloperoxidase (MPO) and decreased HDL-linked paraoxonase-1 (PON1) activity have been reported in dyslipidemic patients. Some changes in HDL subfraction distributions were also studied previously, but data on structural and functional changes in dyslipidemia are not complete. Therefore, the authors aimed to evaluate these qualitative and quantitative markers of HDL in dyslipidemic patients and healthy control subjects. Methods: Anthropometric parameters, serum levels of lipoproteins and MPO, as well as PON1 activities were investigated in 81 untreated dyslipidemic patients and in 32 healthy gender-matched controls. Additionally, HDL subfractions were detected by an electrophoretic method on polyacrylamide gel (Lipoprint). Results: Significantly higher glucose, hemoglobin A1c, total cholesterol, low-density lipoprotein-cholesterol, triglyceride, lipoprotein(a), apolipoprotein B, C-reactive protein, and MPO levels were found in patients compared to the healthy subjects. There were no significant differences in PON1 paraoxonase and arylesterase activities between the two study groups, but MPO/PON1 ratio was significantly higher in patients. There was a shift towards the smaller HDL subfractions, but only the intermediate HDL ratio was significantly lower in patients compared to controls. Conclusion:The results highlight the importance of HDL-associated pro-and antioxidant enzymes suggesting the possible clinical benefit of MPO/PON1 calculation and confirm that quantification of HDL-C level alone provides limited data regarding HDL's cardioprotective effect. Calculation of MPO/PON1 ratio may be a useful cardiovascular marker in dyslipidemia. Key words:High-density lipoprotein, subfraction, paraoxonase, myeloperoxidase, dyslipidemia ABSTRACTArticle history:

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Section: Discussionmentioning

confidence: 99%

HDL subfraction distribution and HDL function in untreated dyslipidemic patients

Harangi¹,

Szentpéteri²,

Nádró³

et al. 2017

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“…Previous data shows that MPO, PON1, and HDL may bind to each other, forming a ternary complex, wherein PON1 partially inhibits MPO activity and MPO inactivates PON1 influencing endogenous oxidative stress and lipid peroxidation during inflammation [ 29 ]. In our previous study PON1 arylesterase activity was found to be an independent predictor of MPO levels in overweight hyperlipidemic, lipid-lowering therapy-naive patients [ 30 ]. In the nondiabetic obese group there were no significant correlations either between paraoxonase activity and myeloperoxidase level or between obestatin and myeloperoxidase level.…”

Section: Discussionmentioning

confidence: 99%

Serum obestatin level strongly correlates with lipoprotein subfractions in non-diabetic obese patients

et al. 2018

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BackgroundObestatin is a ghrelin-associated peptide, derived from preproghrelin. Although many of its effects are unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. To date, level of obestatin and its correlations to the lipid subfractions in non-diabetic obese (NDO) patients have not been investigated.MethodsFifty NDO patients (BMI: 41.96 ± 8.6 kg/m2) and thirty-two normal-weight, age- and gender-matched healthy controls (BMI: 24.16 ± 3.3 kg/m2) were enrolled into our study. Obestatin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions, intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) levels and mean LDL size were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint).ResultsSerum level of obestatin was significantly lower in NDO patients compared to controls (3.01 ± 0.5 vs. 3.29 ± 0.6 μg/ml, p < 0.05). We found significant negative correlations between the level of obestatin and BMI (r = − 0.33; p < 0.001), level of serum glucose (r = − 0.27, p < 0.05), HbA1c (r = − 0.38; p < 0.001) and insulin (r = − 0.34; p < 0.05). Significant positive correlation was found between obestatin level and the levels of ApoA1 (r = 0.25; p < 0.05), large HDL subfraction ratio and level (r = 0.23; p < 0.05 and r = 0.24; p < 0.05), IDL (r = 0.25 p < 0.05) and mean LDL size (r = 0.25; p < 0.05). Serum VLDL ratio and level negatively correlated with obestatin (r = − 0.32; p < 0.01 and r = − 0.21; p = 0.05). In multiple regression analysis obestatin was predicted only by VLDL level.ConclusionsBased on our data, measurement of obestatin level in obesity may contribute to understand the interplay between gastrointestinal hormone secretion and metabolic alterations in obesity.

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“…Furthermore, an elegant study proved the existence of an HDL-MPO-PON1 ternary complex, in which each partner functions as a reciprocal modulator of the other's activity, infl uencing oxidant stress and lipid peroxidation during infl ammation [7]. Our previous study on the same patient population also underlines the importance of this reciprocal inhibition [30].…”

Section: Discussionmentioning

confidence: 77%

Paraoxonase-1 and myeloperoxidase correlate with vascular biomarkers in overweight patients with newly diagnosed untreated hyperlipidaemia

Szentpéteri

Zsíros

Varga

et al. 2017

Vasa

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Summary:Background: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarifi ed. Patients and methods: Serum concentrations of lipid and infl ammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls. Additionally, levels of CD40 ligand (sCD40L) and asymmetric dimethyl arginine (ADMA), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1, and oxidized LDL were determined. Results: We found elevated C-reactive protein (CRP), ADMA, sCD40L, sICAM-1 concentrations, and higher MPO levels in patients with vascular complications compared to those without. The PON1 arylesterase activity correlated negatively with sCD40L, ADMA, and sICAM-1 levels, respectively. In contrast, MPO concentrations showed positive correlations with sCD40L, ADMA, and sICAM-1 levels, respectively. Conclusions: It can therefore be stated that PON1 activity and MPO level correlate strongly with the vascular biomarkers, highlighting the importance of the HDL-associated pro-and antioxidant enzymes in the development of endothelial dysfunction and atherogenesis.Keywords: Paraoxonase, myeloperoxidase, sCD40 ligand, asymmetric dimethyl arginine, soluble intercellular adhesion molecule-1, hyperlipidaemia ties, HDL-associated human paraoxonase-1 (PON1) was shown to prevent the accumulation of lipid peroxides in oxidized LDL and to inactivate bioactive oxidized phospholipids [5,6]. Recent data indicate that MPO, PON1, and HDL may bind to each other, forming a ternary complex, wherein PON1 partially inhibits MPO activity and MPO inactivates PON1 infl uencing endogenous oxidative stress and lipid peroxidation during infl ammation [7].Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is elevated in hypercholesterolaemia [8,9]. Activation of monocytes and polymorphonuclear leukocytes with concomitant release of MPO is regulated in a nitric oxide-dependent fashion. Previous data reveal an ADMA-induced cycle of polymorphonuclear leukocyte activation and enhanced MPO release. These fi ndings highlight the cytokine-like properties of ADMA and also identify MPO as a potential regulatory switch for ADMA bioavailability under infl ammatory conditions [10]. The CD40 Ligand (CD40L) is ubiquitously expressed on cell types that are implicated in infl ammato-

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Paraoxonase-1 arylesterase activity is an independent predictor of myeloperoxidase levels in overweight patients with or without cardiovascular complications

Cited by 14 publications

References 35 publications

HDL subfraction distribution and HDL function in untreated dyslipidemic patients

HDL subfraction distribution and HDL function in untreated dyslipidemic patients

Serum obestatin level strongly correlates with lipoprotein subfractions in non-diabetic obese patients

Paraoxonase-1 and myeloperoxidase correlate with vascular biomarkers in overweight patients with newly diagnosed untreated hyperlipidaemia

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