on September 24, 2009
Published online before print September 24, 2009, doi: 10.1161/ATVBAHA.109.190264
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Submitted on May 7, 2009
Accepted on August 21, 2009
Expression of Human ApoAII in Transgenic Rabbits Leads to Dyslipidemia. A New Model for Combined Hyperlipidemia
Tomonari Koike ;
From the Department of Molecular Pathology (T.K., Y.Y., Y.L., A.B.W., N.S., T.I., Y.W., J.F.), Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan; the Analytical Research Center for Experimental Sciences (S.K., K.N.), Saga University, Japan; the Laboratory Animal Center (E.L.), Xi'an Jiaotong University School of Medicine, China; the Department of Pharmacology (H.S.), Dalian Medical University, China; the Department of Cardiology (B.Z., K.S.), Fukuoka University School of Medicine, Japan; the Department of Lipidology (J.K.), Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; the Department of Rehabilitation (M.M.), Kumamoto Health Science University, Kumamoto, Japan; and the Fukuoka Wajiro Hospital (T.W.), Fukuoka, Japan.
* To whom correspondence should be addressed. E-mail: fan_molpatho{at}yahoo.co.jp.
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 
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.
Key words: apolipoprotein • lipase • transgenic rabbits • hyperlipidemia • HDL
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eLetters:
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- eLetter for Koike et al, ATVB published September 24, 2009, 10.1161/ATVBAHA.109.190264
- Athina D Kalopissis, et al.
- ATVB Online, 19 Nov 2009 [Full text]