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A neutralizing monoclonal antibody doubles HDL cholesteryl ester in rabbits by blocking CETP in vivo (J Clin Invest 1989)
Original title: Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism
Rabbits injected with the neutralizing monoclonal antibody TP1 against CETP (n equals 8), versus irrelevant antibody or saline controls (n equals 8), showed an initial 71% inhibition of CETP activity that fell to 45% by 48 hours. HDL cholesteryl ester rose in the CETP-inhibited animals, doubling initial and control values by 48 hours (P less than 0.001), while HDL triglyceride fell reciprocally with HDL protein unchanged, indicating a cholesteryl ester for triglyceride exchange, and VLDL cholesteryl ester to triglyceride ratio decreased. Using radiolabeled cholesteryl ether HDL as a tracer, CETP inhibition delayed clearance of radioactivity from HDL (control 6.8 versus TP1 4.1 pools/day) and from plasma (7.8 versus 5.2 pools/day), demonstrating that CETP plays a quantitatively important role in HDL cholesteryl ester catabolism in vivo, driving both the exchange of triglyceride for cholesteryl ester and the clearance of cholesteryl ester from plasma.
Original abstract
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.
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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.