LDL particle size in familial combined hyperlipidemia: effects of serum lipids, lipoprotein-modifying enzymes, and lipid transfer proteins.
Small, dense LDL particles are typical for FCHL. Intravascular lipid exchange and net transfer among HDL, LDL, and triglyceride-rich lipoproteins as well as lipolysis in the VLDL-IDL-LDL cascade regulate properties of LDL. We investigated postheparin plasma activities of hepatic lipase (HL) and LPL, and plasma activities of CETP and phospholipid transfer protein (PLTP) in 191 individuals from 37 Finnish FCHL families. LDL peak particle diameter (LDL size) was measured with 2-10% gradient polyacrylamide gel electrophoresis. LDL size was significantly smaller in affected FCHL family members (n = 68) as compared with nonaffected FCHL family members (n = 78) or spouses (n = 45) (25.3 +/- 1.5 nm, 26.8 +/- 1.2 nm, and 26.6 +/- 1.2 nm, respectively, P < 0.001 for both). In affected FCHL family members, serum triglycerides were the strongest correlate for LDL size (r = -0.71, P < 0.001). In univariate correlation analysis LDL size was not associated with HL, LPL, CETP, and PLTP activities. In multivariate stepwise regression analysis, however, serum triglycerides, CETP activity, HL activity, and HDL cholesterol were significant predictors of LDL size in affected FCHL subjects (adjusted r (2) = 0.642). We conclude that serum triglyceride concentration is strongly correlated with LDL size in affected FCHL subjects. After adjustment for serum triglycerides, HL and CETP activities are associated with LDL size in FCHL.
Vakkilainen
Juha
J
Department of Medicine, Helsinki University Central Hospital, Haartmaninkatu 4, P.O. Box 340, 00029 HUCH, Helsinki, Finland.
Jauhiainen
Matti
M
Ylitalo
Kati
K
Nuotio
Ilpo O
IO
Viikari
Jorma S A
JS
Ehnholm
Christian
C
Taskinen
Marja-Riitta
MR
D000328:Adult; D002352:Carrier Proteins / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D010316:Particle Size; D049294:Phospholipid Transfer Proteins; D012044:Regression Analysis; D013223:Statistics as Topic
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL; D006023:Glycoproteins; D008055:Lipids; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D008071:Lipoprotein Lipase