HDL biology
Human ApoC1 transgene reduces atherosclerosis in rabbits partly by inhibiting CETP activity (Atherosclerosis 2021)
Original title: Human apolipoprotein C1 transgenesis reduces atherogenesis in hypercholesterolemic rabbits
Apolipoprotein C1 favours cholesterol accumulation in HDL partly by inhibiting CETP in human plasma, but its net effect on atherosclerosis had not been tested in an animal species that naturally expresses CETP, unlike mice. Researchers generated rabbits expressing a human apoC1 transgene and fed them a cholesterol diet. Compared with wild-type littermates, transgenic rabbits developed significantly less extensive atherosclerosis (minus 22 percent, P less than 0.05) and their HDL was a significantly poorer CETP substrate (minus 25 percent, P less than 0.05), alongside higher HDL cholesterol and PON-1 activity and lower lipid-oxidation markers. Even on standard chow, transgenic rabbits had higher HDL cholesterol and significantly lower CETP activity (cholesteryl ester transfer rate minus 10 percent, specific CETP activity minus 14 percent, both P less than 0.05). The findings show human apoC1 attenuates atherosclerosis at least in part through inhibiting plasma CETP activity.
Original abstract
Background And Aims: Apolipoprotein (apo) C1 is a 6.6 kDa protein associated with HDL and VLDL. ApoC1 alters triglyceride clearance, and it also favors cholesterol accumulation in HDL, especially by inhibiting CETP in human plasma. Apart from studies in mice, which lack CETP, the impact of apoC1 on atherosclerosis in animal models expressing CETP, like in humans, is not known. This study aimed at determining the net effect of human apoC1 on atherosclerosis in rabbits, a species with naturally high CETP activity but with endogenous apoC1 without CETP inhibitory potential.
Methods: Rabbits expressing a human apoC1 transgene (HuApoC1Tg) were generated and displayed significant amounts of human apoC1 in plasma.
Results: After cholesterol feeding, atherosclerosis lesions were significantly less extensive (-22%, p < 0.05) and HDL displayed a reduced ability to serve as CETP substrates (-25%, p < 0.05) in HuApoC1Tg rabbits than in WT littermates. It was associated with rises in plasma HDL cholesterol level and PON-1 activity, and a decrease in the plasma level of the lipid oxidation markers 12(S)-HODE and 8(S)HETE. In chow-fed animals, the level of HDL-cholesterol was also significantly higher in HuApoC1Tg than in WT animals (0.83 ± 0.11 versus 0.73 ± 0.11 mmol/L, respectively, p < 0.05), and it was associated with significantly lower CETP activity (cholesteryl ester transfer rate, -10%, p < 0.05; specific CETP activity, -14%, p < 0.05).
Conclusions: Constitutive expression of fully functional human apoC1 in transgenic rabbit attenuates atherosclerosis. It was found to relate, at least in part, to the inhibition of plasma CETP activity and to alterations in plasma HDL.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.