Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism.
Cholesteryl ester transfer protein (CETP) promotes in vitro transfer of cholesteryl ester (CE) and triglyceride (TG) between lipoproteins. We studied the function of CETP in vivo in rabbit lipoprotein metabolism using a neutralizing monoclonal antibody (MAb, TP1) to CETP. Rabbits were injected with TP1 (n = 8), or irrelevant MAb or saline (control, n = 8), resulting in an initial 71% inhibition of CETP, which fell to 45% after 48 h. HDL CE rose in the inhibited animals, reaching levels that doubled initial and control values at 48 h (P less than 0.001). HDL TG fell reciprocally, but HDL protein did not change, suggesting a CE for TG exchange. VLDL CE/TG decreased. Rabbits were also given [3H]cholesteryl ether HDL (a CE analogue). CETP inhibition delayed the initial clearance of radioactivity from HDL (control 6.8 vs. TP1 4.1 pools/d) and plasma (7.8 vs. 5.2 pools/d). We conclude that CETP plays a quantitatively important role in HDL CE catabolism in the rabbit, promoting the exchange of TG for CE and the clearance of CE from plasma.
Whitlock
M E
ME
Department of Medicine, Columbia University College of Physicians & Surgeons, New York 10032.
Swenson
T L
TL
Ramakrishnan
R
R
Leonard
M T
MT
Marcel
Y L
YL
Milne
R W
RW
Tall
A R
AR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D006023:Glycoproteins; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D011817:Rabbits; D014280:Triglycerides / Q000378:metabolism
D000911:Antibodies, Monoclonal; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides