Human apolipoprotein A-II is a pro-atherogenic molecule when it is expressed in transgenic mice at a level similar to that in humans: evidence of a potentially relevant species-specific interaction with diet.
We report on the effect of human apolipoprotein (apo) A-II transgene expression on atherosclerosis susceptibility in two transgenic lines (25.3 and 11.1) whose plasma human apoA-II concentrations (approximately 23 and 96 mg/dl, respectively) span the normal range in humans. After 9 months of an atherogenic diet, 25.3 and 11.1 transgenic mice developed aortic atherosclerotic lesions that were approximately 1.7- and 7-fold, respectively, more extensive than those of non-transgenic control mice. However, there was no difference in the area of atherosclerosis of transgenic and control mice when fed a regular chow diet This contrasts with the findings in murine apoA-II transgenic mice and provides evidence of a species-specific characteristic that could be of relevance with respect to the high fat intake diets common in most industrialized countries. A possible mechanism of the pro-atherogenic action of human apoA-II could be the inhibition of reverse cholesterol transport and, in support of this, we observed an impairment of apoA-I-HDL particle interconversion in the plasma of 11.1 transgenic mice caused, at least in part, by a marked decrease in the endogenous lecithin:cholesterol acyltransferase activity.
Escolà-Gil
J C
JC
Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Marzal-Casacuberta
A
A
Julve-Gil
J
J
Ishida
B Y
BY
Ordóñez-Llanos
J
J
Chan
L
L
González-Sastre
F
F
Blanco-Vaca
F
F
D000818:Animals; D001018:Aortic Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology; D016632:Apolipoprotein A-I / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000235:genetics* / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D004036:Diet, Atherogenic; D015870:Gene Expression; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D013045:Species Specificity
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase