The effect of lovastatin on the low density lipoprotein metabolism in bypassed rabbits was investigated. Partial ileal bypass effectively reduced total and low density lipoprotein (LDL) cholesterol by 44 and 48% respectively. The LDL drop was due to an increased fractional catabolic rate (FCR) of apolipoprotein B (apo B) from 0.74 to 1.27 pools per day with no effect on the apo B absolute catabolic rate and an increased expression of liver LDL receptors (+71%). Association of lovastatin with PIB resulted in a further decrease of total and LDL cholesterol (56 and 75% respectively) as compared to bypassed animals, without effects on the LDL FCR (1.27 ± 0.11 versus 1.42 ± 0.13 pools/day) or the expression of LDL receptors by the liver. The reduction of LDL was due to a decrease of the apolipoprotein B absolute synthetic rate (8.5 ± 1.7 versus 13.6 ± 1.7 mg/day). From these data we conclude that in bypassed rabbits lovastatin lowers total and LDL cholesterol mainly by reducing apolipoprotein B production rate.
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