Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI
EPIDEMIOLOGICAL surveys have identified a strong inverse relationship between the
amount in the plasma of high density lipoproteins (HDL), apolipoprotein Al (ApoA-I), the
major protein component of HDL, and the risk for atherosclerosis in humans1, 2. It is not
known if this relationship arises from a direct antiatherogenic effect of these plasma
components or if it is the result of other factors also associated with increases in ApoA-I and
HDL levels. Because some strains of mice are susceptible to diet-induced formation of …
amount in the plasma of high density lipoproteins (HDL), apolipoprotein Al (ApoA-I), the
major protein component of HDL, and the risk for atherosclerosis in humans1, 2. It is not
known if this relationship arises from a direct antiatherogenic effect of these plasma
components or if it is the result of other factors also associated with increases in ApoA-I and
HDL levels. Because some strains of mice are susceptible to diet-induced formation of …
Abstract
EPIDEMIOLOGICAL surveys have identified a strong inverse relationship between the amount in the plasma of high density lipoproteins (HDL), apolipoprotein Al (ApoA-I), the major protein component of HDL, and the risk for atherosclerosis in humans1,2. It is not known if this relationship arises from a direct antiatherogenic effect of these plasma components or if it is the result of other factors also associated with increases in ApoA-I and HDL levels. Because some strains of mice are susceptible to diet-induced formation of preatherosclerotic fatty streak lesions, and because of available techniques for the genetic manipulation of this organism, the murine system offers a unique setting in which to investigate the process of early atherogenesis. To test the hypothesis that induction of a high plasma concentration of ApoA-I and HDL would inhibit this process, we studied the effects of atherogenic diets on transgenic mice expressing high amounts of human ApoA-I. We report that transgenic mice with high plasma ApoA-I and HDL levels were significantly protected from the development of fatty streak lesions.
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