Atherogenesis in transgenic mice expressing human apolipoprotein(a)
Elevated plasma levels of the lipoprotein Lp(a) are associated with increased risk for atherosclerosis and its manifestations, myocardial infarction, stroke and restenosis (for reviews, see refs 1-3). Lp(a) differs from low-density lipoprotein by the addition of the glycoprotein apolipoprotein(a), a homologue of plasminogen that contains many tandemly repeated units which resemble the fourth kringle domain of plasminogen, and single homologues of its kringle-5 and protease domain. As plasma Lp(a) concentration is strongly influenced by heritable factors and is refractory to most drug and dietary manipulation, the effects of modulating it are difficult to mimic experimentally. In addition, the absence of apolipoprotein(a) from virtually all species other than primates precludes the use of convenient animal models. Here we show that transgenic mice expressing human apolipoprotein(a) are more susceptible than control mice to the development of lipid-staining lesions in the aorta, and that apolipoprotein(a) co-localizes with lipid deposition in the artery walls.
Lawn
R M
RM
Division of Cardiovascular Medicine, Stanford University School of Medicine, California 94305.
Wade
D P
DP
Hammer
R E
RE
Chiesa
G
G
Verstuyft
J G
JG
Rubin
E M
EM
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001053:Apolipoproteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D053241:Apoprotein(a); D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics; D004036:Diet, Atherogenic; D006801:Humans; D015151:Immunoblotting; D017270:Lipoprotein(a); D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012016:Reference Values
D001053:Apolipoproteins; D017270:Lipoprotein(a); D004247:DNA; D053241:Apoprotein(a)