Bezafibrate increases prebeta 1-HDL at the expense of HDL2b in hypertriglyceridemia.
Prebeta1-high density lipoprotein (prebeta1-HDL), the initial acceptor of cell-derived cholesterol, can be generated from HDL(2) by hepatic lipase. Because bezafibrate elevates lipase activity, it may increase prebeta1-HDL at the expense of HDL(2). To answer this question, we determined the apolipoprotein A-I (apoA-I) distribution in 20 hypertriglyceridemics (triglycerides>2.26 mmol/L) and 20 sex-matched normolipidemics by native 2-dimensional gel electrophoresis. At baseline, prebeta1-HDL was 70% higher in hypertriglyceridemics than in normolipidemics (123.5+/-49.9 versus 72.5+/-34.1 mg/L apoA-I, P<0.01). Prebeta1-HDL was positively correlated with triglyceride (r=0.624, P<0.0001). A 4-week bezafibrate treatment (400 mg daily) increased prebeta1-HDL by 30% (160.2+/-64.5 mg/L apoA-I, P<0.05) but decreased HDL(2b) by 31% (from 188.8+/-94.9 to 129.3+/-78.7 mg/L apoA-I, P<0.05). Hepatic lipase activity increased by 24% (P<0.005). Prebeta1-HDL was generated either from ultracentrifugally isolated HDL(2) or from plasma during incubation with triglyceride lipase. In conclusion, bezafibrate increases prebeta1-HDL at the expense of HDL(2). We speculate that such an effect might partly contribute to the antiatherogenic action of bezafibrate.
Miida
T
T
Department of Laboratory Medicine, First Niigata University School of Medicine, Niigata, Japan. miida@med.niigata-u.ac.jp
Sakai
K
K
Ozaki
K
K
Nakamura
Y
Y
Yamaguchi
T
T
Tsuda
T
T
Kashiwa
T
T
Murakami
T
T
Inano
K
K
Okada
M
M
D000328:Adult; D001629:Bezafibrate / Q000494:pharmacology*; D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006023:Glycoproteins; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000188:drug therapy* / Q000201:enzymology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008049:Lipase / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood* / Q000302:isolation & purification; D053439:Lipoproteins, HDL2; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D014280:Triglycerides / Q000097:blood
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D053442:High-Density Lipoproteins, Pre-beta; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; D014280:Triglycerides; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008049:Lipase; D001629:Bezafibrate