ALTERED APOLIPOPROTEIN-B METABOLISM IN VERY-LOW-DENSITY LIPOPROTEIN FROM LOVASTATIN-TREATED GUINEA-PIGS

Previous studies have shown that treatment of guinea pigs with lovasta tin alters the composition and the metabolic properties of circulating low density lipoprotein (LDL). Specifically, LDL isolated from lovast atin-treated animals is cleared from plasma more slowly than LDL isola ted from control animals, when injected into the guinea pig. In the pr esent study, we examine whether lovastatin also affects the metabolic properties of very low density lipoprotein (VLDL), the metabolic precu rsor of LDL. VLDL isolated from lovastatin-treated guinea pigs (L-VLDL ) and VLDL isolated from untreated (control) guinea pigs (C-VLDL) were radioiodinated and simultaneously injected into eight untreated guine a pigs. Radioactivity as sociated with apolipoprotein B-100 (apoB) was measured in four plasma density fractions and analyzed using a compar tmental model consisting of fast and slow pools for VLDL, fast and slo w pools for intermediate density lipoprotein (IDL), and a single slow pool for LDL. The fractional catabolic rate (FCR) for C-VLDL apoB was 2.8 +/- 1.0 h(-1) and for L-VLDL apoB was 5.1 +/- 2.0 h(-1) (P < 0.002 , paired t test). The fractions of control and lovastatin VLDL apoB co nverted to LDL averaged 0.15 +/- 0.15 and 0.02 +/- 0.02, respectively (P < 0.05, paired t test). Finally, the FCRs of LDL apoB derived from control and lovastatin VLDL were similar (0.059 +/- 0.007 h(-1) and 0. 083 +/- 0.038 h(-1), respectively; paired t test not significant). The se data indicate that L-VLDL was irreversibly removed from the plasma of an untreated guinea pig more rapidly than was C VLDL. Thus, the met abolic behavior of VLDL apoB is affected by lovastatin. Therefore, cha nges in lipoprotein particles themselves must be considered in assessi ng the overall impact of treatment with lovastatin.