Expression of human apoAII in transgenic rabbits leads to dyslipidemia: a new model for combined hyperlipidemia.

Abstract

OBJECTIVE:

Apolipoprotein AII (apoAII) is the second major apolipoprotein in high-density lipoprotein (HDL). However, the physiological functions of apoAII in lipoprotein metabolism have not been fully elucidated.

METHODS AND RESULTS:

We generated human apoAII transgenic (Tg) rabbits, a species that normally does not have an endogenous apoAII gene. Plasma levels of human apoAII in Tg rabbits were approximately 30 mg/dL, similar to the plasma levels in healthy humans. The expression of human apoAII in Tg rabbits resulted in increased levels of plasma triglycerides, total cholesterol, and phospholipids accompanied by a marked reduction in HDL-cholesterol levels compared with non-Tg littermates. Analysis of lipoprotein fractions showed that hyperlipidemia exhibited by Tg rabbits was caused by elevated levels of very-low-density lipoproteins (VLDL) and intermediate-density lipoproteins. Furthermore, postheparin lipoprotein lipase activity significantly decreased in Tg rabbits compared with non-Tg rabbits.

CONCLUSIONS:

These results indicate that apoAII plays an important role in both VLDL and HDL metabolism, possibly through the inhibition of lipoprotein lipase activity. ApoAII Tg rabbits may become a new model for the study of human familial combined hyperlipidemia.

• Authors: Tomonari Koike, Shuji Kitajima, Ying Yu, Ying Li, Kazutoshi Nishijima, Enqi Liu, Huijun Sun, Ahmed Bilal Waqar, Nobumitsu Shibata, Tomoriho Inoue, Yao Wang, Bo Zhang, Junji Kobayashi, Masatoshi Morimoto, Keijiro Saku, Teruo Watanabe, Jianglin Fan
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 29 Issue 12 Pg. 2047-53 (Dec 2009) ISSN: 1524-4636 [Electronic] United States
• PMID: 19778946 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein A-II
• Cholesterol, HDL
• Lipoproteins, IDL
• Lipoproteins, VLDL
• Recombinant Proteins
• Triglycerides
• Cholesterol
• Lipoprotein Lipase

Topics

• Animals
• Animals, Genetically Modified
• Apolipoprotein A-II (blood, genetics, metabolism)
• Cholesterol (blood)
• Cholesterol, HDL (blood)
• Disease Models, Animal
• Gene Expression
• Humans
• Hyperlipidemia, Familial Combined (blood, etiology, genetics)
• Lipoprotein Lipase (blood)
• Lipoproteins, IDL (blood)
• Lipoproteins, VLDL (blood)
• Liver (metabolism)
• Rabbits
• Recombinant Proteins (blood, genetics)
• Triglycerides (blood)