The elevation of apoB in hypercholesterolemic patients is primarily attributed to the relative increase of apoB/Lp-PLA2

Constantinos C Tellis,Eliza Moutzouri,Moses Elisaf,Robert L Wolfert,Alexandros D Tselepis

doi:10.1194/jlr.m041806

Constantinos C Tellis, Eliza Moutzouri + Show 3 more

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https://doi.org/10.1194/jlr.m041806

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Abstract

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a risk factor of cardiovascular disease. Plasma Lp-PLA₂ is mainly associated with apolipoprotein (apo)B-containing lipoproteins, primarily with low density lipoproteins (LDLs). Importantly, only a proportion of circulating lipoproteins contain Lp-PLA₂. We determined the plasma levels of Lp-PLA₂-bound apoB (apoB/Lp-PLA₂) in patients with primary hypercholesterolemia. The effect of simvastatin therapy was also addressed. The plasma apoB/Lp-PLA₂ concentration in 50 normolipidemic controls and 53 patients with primary hypercholesterolemia at baseline and at 3 months posttreatment with simvastatin (40 mg/day) was determined by an enzyme-linked immunosorbent assay. The concentration of the apoB-containing lipoproteins that do not bind Lp-PLA₂ [apoB/Lp-PLA₂⁻] was calculated by subtracting the apoB/Lp-PLA₂ from total apoB. The apoB/Lp-PLA₂ levels were 3.6-fold higher, while apoB/Lp-PLA₂⁻ were 1.3-fold higher in patients compared with controls. After 3 months of simvastatin treatment apoB/Lp-PLA₂ and apoB/Lp-PLA₂⁻ levels were reduced by 52% and 33%, respectively. The elevation in apoB-containing lipoproteins in hypercholesterolemic patients is mainly attributed to the relative increase in the proatherogenic apoB/Lp-PLA₂, while simvastatin reduces these particles to a higher extent compared with apoB/Lp-PLA₂⁻. Considering that Lp-PLA₂ is proatherogenic, the predominance of apoB/Lp-PLA₂ particles in hypercholesterolemic patients may contribute to their higher atherogenicity and incidence of cardiovascular disease.

Highlights

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor of cardiovascular disease
Hypercholesterolemic patients exhibited significantly higher body mass index values as well higher serum levels of total cholesterol, low density lipoproteins (LDLs)-cholesterol, oxidized LDL (oxLDL), and high sensitivity C-reactive protein (hsCRP) compared with controls
Hypercholesterolemic patients exhibited higher levels of buoyant LDL-cholesterol and small dense LDL (sdLDL)-cholesterol compared with controls, whereas no difference in the TGs, Lp(a), sdLDL proportion, and mean LDL size was observed between the two study groups (Table 1). apolipoprotein B (apoB) as well as lipoproteinassociated phospholipase A2 (Lp-PLA2) activity and mass levels were significantly higher in hypercholesterolemic patients compared with controls, whereas no difference in the ratio of Lp-PLA2 mass/apoB was observed between hypercholesterolemic patients and controls (Table 1)

Summary

Introduction

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor of cardiovascular disease. We determined the plasma levels of Lp-PLA2-bound apoB (apoB/Lp-PLA2) in patients with primary hypercholesterolemia. The plasma apoB/Lp-PLA2 concentration in 50 normolipidemic controls and 53 patients with primary hypercholesterolemia at baseline and at 3 months posttreatment with simvastatin (40 mg/day) was determined by an enzyme-linked immunosorbent assay. The elevation in apoB-containing lipoproteins in hypercholesterolemic patients is mainly attributed to the relative increase in the proatherogenic apoB/Lp-PLA2, while simvastatin reduces these particles to a higher extent compared with apoB/Lp-PLA2(؊). Considering that LpPLA2 is proatherogenic, the predominance of apoB/Lp-PLA2 particles in hypercholesterolemic patients may contribute to their higher atherogenicity and incidence of cardiovascular disease.—Tellis, C. The total Lp-PLA2 plasma enzyme has been determined; this mainly represents the LDL-associated Lp-PLA2.

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