Human apolipoprotein C1 transgenesis reduces atherogenesis in hypercholesterolemic rabbits

Background and aimsApolipoprotein (apo) C1 is a 6.6 kDa protein associated with HDL VLDL. ApoC1 alters triglyceride clearance, it also favors cholesterol accumulation in HDL, especially by inhibiting CETP human plasma. Apart from studies mice, which lack CETP, the impact of apoC1 on atherosclerosis animal models expressing like humans, not known. This study aimed at determining net effect rabbits, species naturally high activity but endogenous without inhibitory potential.MethodsRabbits transgene (HuApoC1Tg) were generated displayed significant amounts plasma.ResultsAfter feeding, lesions significantly less extensive (?22%, p < 0.05) reduced ability to serve as substrates (?25%, HuApoC1Tg rabbits than WT littermates. It was rises plasma level PON-1 activity, decrease lipid oxidation markers 12(S)-HODE 8(S)HETE. In chow-fed animals, HDL-cholesterol higher animals (0.83 ± 0.11 versus 0.73 mmol/L, respectively, 0.05), lower (cholesteryl ester transfer rate, ?10%, 0.05; specific ?14%, 0.05).ConclusionsConstitutive expression fully functional transgenic rabbit attenuates atherosclerosis. found relate, least part, inhibition alterations HDL.