Lysophosphatidylcholine contents in plasma LDL in patients with type 2 diabetes mellitus: relation with lipoprotein-associated phospholipase A2 and effects of simvastatin treatment.

Masanori Iwase, Kazuo Sonoki, Nobuhiro Sasaki, Shigehiro Ohdo, Shun Higuchi, Hiroaki Hattori, Mitsuo Iida

Index: Atherosclerosis 196(2) , 931-6, (2008)

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Abstract

Increased lipoprotein-associated PLA(2) (Lp-PLA(2)) predicts the future development of cardiovascular diseases. Although lysophosphatidylcholine (lyso-PC) produced by Lp-PLA(2) may contribute to its proatherogenic activity, the relation between Lp-PLA(2) and lyso-PC content in LDL remains unclarified. We determined the correlation between lyso-PC content in LDL and serum concentrations of Lp-PLA(2), chemokines, oxidative and inflammatory markers and microvascular complications in 32 patients with type 2 diabetes mellitus free of macroangiopathy. We also investigated the effect of simvastatin treatment on Lp-PLA(2) and lyso-PC content in 26 hypercholesterolemic patients with type 2 diabetes mellitus. 1-palmitoyl lyso-PC was measured using electrospray ionization-liquid chromatography/mass spectrometry and Lp-PLA(2) by ELISA. Lyso-PC content in LDL was significantly higher in diabetic patients than in control healthy subjects. Lyso-PC content correlated significantly with Lp-PLA(2) levels (r=0.56, p<0.0001), and was significantly higher in patients with preproliferative or proliferative retinopathy and those with nephropathy than the control. Simvastatin treatment reduced serum Lp-PLA(2) and lyso-PC content in LDL. Our findings suggest that Lp-PLA(2) has the proatherogenic activity by contributing to the production of lyso-PC in circulating LDL.