Effect of gemfibrozil on the regulation of HDL subfractions in hypertriglyceridaemic patients.
OBJECTIVE
To study changes of HDL subfractions and their regulation during gemfibrozil treatment in hypertriglyceridaemia.


METHODS
Twenty patients with hypertriglyceridaemia were randomized to receive either 1200 mg day-1 gemfibrozil or placebo for 3 months. After a 6-week, single-blind placebo period, the patients were randomized to receive either gemfibrozil or placebo for 3 months in a double-blind study.


METHODS
The patients were studied as outpatients in the Third Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.


METHODS
Ultracentrifugally isolated HDL subclasses; concentrations of apoA-I, apoA-II, LpA-I and LpA-I:A-II particles; post-heparin plasma lipoprotein lipase (LPL), hepatic lipase (HL) and plasma cholesteryl ester transfer protein (CETP) activities; phospholipid transfer protein (PLTP) and lecithine cholesteryl acyltransferase (LCAT) activities were measured in plasma from six patients from both groups.


RESULTS
Gemfibrozil increased the concentration of HDL cholesterol (+11.1%) because of the rise of HDL3 cholesterol (34.5%, P < 0.01). The concentration of LpA-I particles was reduced during gemfibrozil treatment (-12.4%, P < 0.05), while that of apoA-II increased (+12.3%, P < 0.01). The LpA-I to LpA-I:A-II ratio decreased significantly in the gemfibrozil group (-18.9%, P < 0.01). Gemfibrozil increased LPL and HL activities by 18.2% (P < 0.05) and by 19.6%, respectively. Plasma CETP activity was also increased during gemfibrozil treatment (+15.8%, P < 0.05).


CONCLUSIONS
The gemfibrozil-induced elevation of HDL3 and apoA-II may reflect the combined action of LPL, HL and CETP on plasma HDL metabolism.
Kahri
J
J
Third Department of Medicine, Helsinki University, Finland.
Sane
T
T
van Tol
A
A
Taskinen
M R
MR
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D001053:Apolipoproteins / Q000097:blood; D017301:Ca(2+) Mg(2+)-ATPase / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D015248:Gemfibrozil / Q000008:administration & dosage / Q000627:therapeutic use*; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids / Q000097:blood; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D006023:Glycoproteins; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D014280:Triglycerides; D017301:Ca(2+) Mg(2+)-ATPase; D015248:Gemfibrozil