The hypolipidemic action of bezafibrate therapy in hypertriglyceridemia ismediated by upregulation of lipoprotein lipase: no effects on VLDL substrate affinity to lipolysis or LDL receptor binding
Fhaf. De Man et al., The hypolipidemic action of bezafibrate therapy in hypertriglyceridemia ismediated by upregulation of lipoprotein lipase: no effects on VLDL substrate affinity to lipolysis or LDL receptor binding, ATHEROSCLER, 153(2), 2000, pp. 363-371
Citations number
42
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Fibrates are regarded as drugs of choice in hypertriglyceridemia (HTG). Dow
nregulation of apolipoprotein (apo) C-III gene expression and upregulation
of lipoprotein lipase (LPL) gene expression have been suggested to explain
the hypolipidemic action of fibrates. This study was designed to study the
effects of bezafibrate therapy on very low density lipoprotein (VLDL) susce
ptibility to lipolysis, VLDL binding to the low density lipoprotein (LDL) r
eceptor and postheparin LPL activities in patients with HTG. VLDL lipolysis
was studied with heparan sulfate proteoglycan-bound LPL. Binding affinity
of VLDL to the LDL receptor was determined in J774 cells with I-125-labeled
control LDL, Eighteen HTG patients were randomized to receive, in a double
-blind placebo-controlled cross-over fashion, 400 mg bezafibrate once daily
for 6 weeks. In response to bezafibrate therapy, plasma triglyceride and a
poC-III levels decreased by 69 and 42%, respectively. HTG VLDL was lipolyze
d less efficiently compared to control VLDL, and lipolysis did not improve
by bezafibrate therapy. VLDL binding affinity to the LDL receptor was compa
rable between the control group and HTG group, and did not change upon beza
fibrate therapy. However, the post-heparin LPL activity in the HTG patients
increased from 153 to 192 U/1 (P = 0.025). A strong inverse relation was o
bserved between the change in LPL activities and the change in triglyceride
levels (I = - 0.62, P = 0.006). In conclusion, the hypolipidemic action of
bezafibrate therapy in HTG may be attributed to increased LPL activity, wh
ereas VLDL susceptibility to lipolysis and LDL receptor binding are not aff
ected. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.