TY - JOUR
T1 - 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
AU - Escolá-Gil, Joan Carles
AU - Marzal-Casacuberta, Àfrica
AU - Julve-Gil, Josep
AU - Ishida, Brian Y.
AU - Ordóñez-Llanos, Jordi
AU - Chan, Lawrence
AU - González-Sastre, Francesc
AU - Blanco-Vaca, Francisco
PY - 1998/2/1
Y1 - 1998/2/1
N2 - 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 (~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 ~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.
AB - 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 (~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 ~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.
KW - Apolipoprotein A- I
KW - Atherosclerosis
KW - High density lipoproteins
KW - Lecithin:cholesterol acyltransferase
M3 - Article
VL - 39
SP - 457
EP - 462
IS - 2
ER -