Enhancement of cholesteryl ester transfer in plasma by hormone-replacement therapy.
To study possible mechanisms for the suggested protective effect of hormone-replacement therapy (HRT) with respect to cardiovascular disease we investigated lipoprotein parameters, mass and activity of lipoprotein-metabolizing enzymes, magnitude of postprandial lipemia, and vascular endothelial function in 13 postmenopausal women. All patients were examined before and 3 months after implementation of HRT with estrogen alone (group A, n = 6) or estrogen plus gestagen (group B, n = 7). HRT (groups A and B) resulted in enhanced total transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins (56% +/- 11.45% v 50.82% +/- 13.68%, P <.05) and increased apoA-I plasma concentration (171 +/- 30 v 147 +/- 22 mg/dL, P <.05). Fasting triglycerides (TG) were increased (134 +/- 40 v 115 +/- 39 mg/dL, P <.05). In group A patients the magnitude of postprandial lipemia increased significantly (1,737 +/- 756 v 1,475 +/- 930 mg TG/dL plasma/8 h, P <.05) without any change in lipoprotein lipase (LPL) activity, but with a concomitant decrease in low-density lipoprotein (LDL) size. In both groups flow-mediated dilation (FMD) reflecting vascular endothelial function was not influenced, suggesting that HRT may not directly affect vascular function but rather alters lipoprotein metabolism. The increase of apoA-I was not accompanied by an equivalent rise of HDL cholesterol. Based on the present data this finding can be readily explained by an increase in CE transfer from HDL to TG-rich lipoproteins, which is not due to increased cholesteryl ester transfer protein (CETP) plasma levels, but rather reflects an increase in fasting and postprandial TG. In conclusion, the net effect of accelerated CE transfer due to HRT depends on the balance of proatherogenic aspects, like the generation of small dense LDL, and antiatherogenic aspects, like the stimulation of reverse cholesterol transport.
Ritsch
Andreas
A
Department of Medicine, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Kaser
Susanne
S
Volgger
Birgit
B
Abfalter
Elisabeth
E
Sturm
Wolfgang
W
Gänzer
Hannes
H
Föger
Bernhard
B
Kirchmair
Rudolf
R
Ebenbichler
Christoph
C
Patsch
Josef R
JR
D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001057:Apolipoproteins E / Q000235:genetics; D001692:Biological Transport; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002352:Carrier Proteins / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology; D015914:Estrogen Replacement Therapy; D005260:Female; D005502:Food; D005838:Genotype; D006023:Glycoproteins; D006801:Humans; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D010316:Particle Size; D049294:Phospholipid Transfer Proteins; D017698:Postmenopause; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D006023:Glycoproteins; D008055:Lipids; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D014280:Triglycerides; D008071:Lipoprotein Lipase