Distribution of Paraoxonase-1 (PON-1) and Lipoprotein Phospholipase A2 (Lp-PLA2) across Lipoprotein Subclasses in Subjects with Type 2 Diabetes.

Angelina Passaro,Giuseppe Valacchi,Gloria Bonaccorsi,Juana M Sanz,Giovanni Battista Vigna,Arianna Romani,Carlo Cervellati,Carlotta Cavicchio

doi:10.1155/2018/1752940

Angelina Passaro, Giuseppe Valacchi + Show 6 more

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https://doi.org/10.1155/2018/1752940

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Abstract

Paraoxonase-1 (PON1) and lipoprotein phospholipase A2 (Lp-PLA2) may exert an important protective role by preventing the oxidative transformation of high- and low-density lipoproteins (HDL and LDL, respectively). The activity of both enzymes is influenced by lipidome and proteome of the lipoprotein carriers. T2DM typically presents significant changes in the molecular composition of the lipoprotein subclasses. Thus, it becomes relevant to understand the interaction of PON1 and Lp-PLA2 with the subspecies of HDL, LDL, and other lipoproteins in T2DM. Serum levels of PON1-arylesterase and PON1-lactonase and Lp-PLA2 activities and lipoprotein subclasses were measured in 202 nondiabetic subjects (controls) and 92 T2DM outpatients. Arylesterase, but not lactonase or Lp-PLA2 activities, was inversely associated with TD2M after adjusting for potential confounding factors such as age, sex, smoking, body mass index, hypertension, and lipoprotein subclasses (odds ratio = 3.389, 95% confidence interval 1.069–14.756). Marked difference between controls and T2DM subjects emerged from the analyses of the associations of the three enzyme activities and lipoprotein subclasses. Arylesterase was independently related with large HDL-C and small intermediate-density lipoprotein cholesterol (IDL-C) in controls while, along with lactonase, it was related with small low-density lipoprotein cholesterol LDL-C, all IDL-C subspecies, and very low-density lipoprotein cholesterol (VLDL-C) in T2DM (p < 0.05 for all). Concerning Lp-PLA2, there were significant relationships with small LDL-C, large IDL-C, and VLDL-C only among T2DM subjects. Our study showed that T2DM subjects have lower levels of PON1-arylesterase compared to controls and that T2DM occurrence may coincide with a shift of PON1 and Lp-PLA2 towards the more proatherogenic lipoprotein subclasses. The possibility of a link between the two observed phenomena requires further investigations.

Highlights

Several lines of evidence clearly suggest that oxidative stress (OxS) is implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and plays a critical role in the development of its frequent microvascular and macrovascular complications [1]
Arylesterase was independently related with large high-density lipoproteins (HDLs)-C and small intermediate-density lipoprotein cholesterol (IDL-C) in controls while, along with lactonase, it was related with small low-density lipoprotein cholesterol LDL-C, all IDL-C subspecies, and very low-density lipoprotein cholesterol (VLDL-C) in T2DM (p < 0 05 for all)
Our study showed that T2DM subjects have lower levels of PON1-arylesterase compared to controls and that T2DM occurrence may coincide with a shift of PON1 and lipoprotein-associated phospholipase A2 (Lp-PLA2) towards the more proatherogenic lipoprotein subclasses

Summary

Introduction

Several lines of evidence clearly suggest that oxidative stress (OxS) is implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and plays a critical role in the development of its frequent microvascular and macrovascular complications [1]. Increase in ROS results in the accumulation of oxidativedamaged biomolecules, including the highly proatherogenic oxidized low-density lipoproteins (ox-LDLs) [3, 4] These modified lipoproteins entail endothelial cell activation, dysfunction, and death and contribute to the onset and progression of the atherosclerotic process [4]. A wealth of in vitro and in vivo evidence suggests that paraoxonase 1 (PON1) and lipoprotein-associated phospholipase A2 (Lp-PLA2) contribute to vasculoprotective function of HDL [7,8,9,10] Both enzymes are able to hydrolyze, by different and still poorly known mechanisms, lipo-lactones, such as those resulting from oxidation of fatty acid or cholesterolenriching lipid environment of HDL and LDL [7, 9, 11]. It has been suggested that the antioxidant-like function of PON1 and Lp-PLA2 may account for the several findings linking altered levels of enzyme activities and the risk of developing T2DM as well as its related clinical complications [12,13,14,15,16,17]

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