Editorial |
From the Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Correspondence to Shun Ishibashi, MD, PhD, Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail ishibash-tky@umin.ac.jp
Key Words: lipoprotein(a) apolipoprotein(a) atherosclerosis transgenic rabbit
Lipoprotein(a)
[Lp(a)] is composed of 1 particle of LDL attached to apo(a), a
glycoprotein that has striking homology to
plasminogen and tremendous size
heterogeneity owing to the presence of multiple repeats
of plasminogen-like kringle 4 modules (see References 1 and
21 2 for a review). Since Lp(a) was discovered by Berg, numerous
cross-sectional and prospective studies have revealed associations
between high plasma levels of Lp(a) and atherosclerotic vascular
diseases, such as coronary heart disease and stroke (see
References 1 and 31 3 for a review). Although several pathogenic roles for
Lp(a) have been proposed, it has not been completely elucidated how
high Lp(a) levels are associated with vascular diseases. Transgenic
animal models give invaluable means to provide answers to the
intractable question of whether high Lp(a) causes
atherosclerosis and not vice versa. Lawn and
colleagues4 first reported
the generation of apo(a) transgenic mice in 1992. Fatty streak lesion
formation in the aortic sinus of these mice was substantially increased
compared with that of the nontransgenic controls when fed an
atherogenic diet. However, another laboratory failed to reproduce the
atherogenic effects of the overexpressed apo(a) with or without the
overexpressed human apoB-100, even though the same transgene was
used.5 6 It may be
possible that a certain strain of mouse is resistant to the
atherogenic effects of apo(a). In this context, apo(a) transgenic
rabbits have emerged as an alternative model in which the
atherogenicity of apo(a) as well as that of Lp(a) can be reasonably
reevaluated. Recently, 2 lines of apo(a) transgenic rabbits have
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