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Journal of Lipid Research, Vol. 42, 241-248, February 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

ApoA-II expression in CETP transgenic mice increases VLDL production and impairs VLDL clearance

Correspondence to: Francisco Blanco-Vaca, at Hospital de la Santa Creu i Sant Pau, Servei de Bioquímica, C/ Antoni M. Claret, 167, 08025 Barcelona, Spain., fblanco{at}santpau.es (E-mail)

Apolipoprotein (apo)A-II is a major high density lipoprotein (HDL) protein; however, its role in lipoprotein metabolism is largely unknown. Transgenic (Tg) mice that overexpress human apoA-II present functional lecithin: cholesterol acyltransferase deficiency, HDL deficiency, hypertriglyceridemia and, when fed an atherogenic diet, increased non-HDL cholesterol and increased susceptibility to atherosclerosis. In contrast to humans, mice do not present cholesteryl ester transfer protein (CETP) activity in plasma. To study the in vivo interaction of these two proteins, we crossbred human apoA-II and CETP-Tg mice. CETPxapoA-II-Tg mice fed an atherogenic diet, compared with CETP-Tg mice presented a 2-fold decrease in HDL cholesterol and a quantitatively similar increase in total plasma cholesterol and percentage of free cholesterol, non-HDL cholesterol, and free fatty acids, together with a remarkable 112-fold increase in plasma triglycerides. Plasma triglycerides in CETPxapoA-II-Tg mice were mainly associated with very low density lipoproteins (VLDL), which were also enriched in protein content, and resulted from a combination of higher production rate compared with both of their progenitors and non-Tg control mice, and decreased catabolism compared only with CETP-Tg mice.

These results show CETPxapoA-II-Tg mice to be a good model with which to study mechanisms leading to VLDL overproduction and suggest that CETP and, in particular apoA-II, may play a role in the regulation of VLDL metabolism. — Escolà-Gil, J. C., J. Julve, À. Marzal-Casacuberta, J. Ordóñez-Llanos, F. González-Sastre, and F. Blanco-Vaca. ApoA-II expression in CETP transgenic mice increases VLDL production and impairs VLDL clearance. J. Lipid Res. 2001. 42: 241;–248.

Supplementary key words: atherosclerosis, cholesteryl ester transfer protein, high density lipoprotein, hypertrygliceridemia, very low density lipoprotein, familial combined hyperlipidemia

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