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Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:2047-2053
Published online before print September 24, 2009, doi: 10.1161/ATVBAHA.109.190264
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:2047.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Expression of Human ApoAII in Transgenic Rabbits Leads to Dyslipidemia

A New Model for Combined Hyperlipidemia

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

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.

Correspondence to Jianglin Fan, MD, PhD, Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo-City, Yamanashi 409-3898, Japan. 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 {approx}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.

In this study, we generated transgenic rabbits expressing human apoAII and found that expression of human apoAII resulted in elevated plasma levels of triglycerides, total cholesterol, and phospholipids accompanied by reduced plasma HDL-C. Human apoAII transgenic rabbits may become a useful model for the study of combined hyperlipidemia.


Key Words: apolipoprotein • lipase • transgenic rabbits • hyperlipidemia • HDL


Related Article:

ApoAII Controversy Still in Rabbit?
Hitoshi Shimano
Arterioscler Thromb Vasc Biol 2009 29: 1984-1985. [Extract] [Full Text] [PDF]



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]

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