Lysophosphatidylcholine contents in plasma LDL in patients with type 2 diabetes mellitus: relation with lipoprotein-associated phospholipase A2 and effects of simvastatin treatment.
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.
Iwase
Masanori
M
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. iwase@intmed2.med.kyushu-u.ac.jp
Sonoki
Kazuo
K
Sasaki
Nobuhiro
N
Ohdo
Shigehiro
S
Higuchi
Shun
S
Hattori
Hiroaki
H
Iida
Mitsuo
M
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003928:Diabetic Nephropathies / Q000097:blood; D003930:Diabetic Retinopathy / Q000097:blood; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000097:blood*; D008244:Lysophosphatidylcholines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; C006065:We 201; D019821:Simvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase