Action of ciprofibrate in type IIb hyperlipoproteinemia: modulation of the atherogenic lipoprotein phenotype and stimulation of high-density lipoprotein-mediated cellular cholesterol efflux.
The effects of ciprofibrate (100 mg/d) on apolipoprotein (apo)B- and apoAI-containing lipoprotein subclasses, cholesteryl ester (CE) transfer protein activity, and plasma high-density lipoprotein (HDL)-mediated cellular cholesterol efflux were evaluated in 10 patients displaying type IIB hyperlipidemia. Plasma concentrations of large very low-density lipoprotein (VLDL)-1 (Sf 60-400) and of small VLDL-2 (Sf 20-60) were markedly diminished after fibrate treatment (-40%, P = 0.001; and -25%, P = 0.003, respectively). We observed a reduction (-17%; P = 0.005) in plasma low-density lipoprotein (LDL) levels resulting from significant reductions in concentrations of dense LDL particles (-46%; P < 0.0001). Ciprofibrate induced elevation in plasma total HDL (+13%; P = 0.005) levels; such elevation occurred preferentially in HDL-3 (+22%; P = 0.009). Marked reduction in numbers of atherogenic apoB100-containing particle acceptors was associated with a 25% decrease (P < 0.02) in CE transfer protein-mediated CE transfer from HDL. Finally, a significant fibrate-mediated elevation (+13%; P = 0.01 compared with baseline) in the capacity of plasma from type IIB subjects to mediate free cholesterol efflux from scavenger receptor class B, type I-expressing Fu5AH hepatoma cells was observed. In conclusion, the action of ciprofibrate in type IIB dyslipidemia leads to preferential reduction in particle numbers of atherogenic VLDL-1, VLDL-2, and dense LDL and, concomitantly, to elevation in HDL-3 levels that are associated with stimulation of HDL-mediated cellular free cholesterol efflux through the scavenger receptor class B, type I receptor pathway.
Guerin
Maryse
M
Institut National de la Santé et de la Recherche Médicale Unité 551, Dyslipoproteinemia and Atherosclerosis, Hôpital de la Pitié, 75651 Paris, France. mguerin@infobiogen.fr
Le Goff
Wilfried
W
Frisdal
Eric
E
Schneider
Séverine
S
Milosavljevic
Dragana
D
Bruckert
Eric
E
Chapman
M John
MJ
D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy*; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000097:blood; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D058607:Fibric Acids; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood* / Q000235:genetics; D008075:Lipoproteins, HDL / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000097:blood; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D010641:Phenotype; D051381:Rats; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D002788:Cholesterol Esters; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D002995:Clofibric Acid; D002784:Cholesterol; D000242:Cyclic AMP; C019304:ciprofibrate