"EFFECT OF PROGESTERONE AND LOVASTATIN ON THE SECRETION OF VERY LOW DENSITY LIPOPROTEIN 1 AND 2 IN THE NORMAL GUINEA PIG MODEL"

Abstract

Liver secretes a large range of very low density lipoprotein (VLDL) particles of different sizes and Svedberg flotation rates (Sf). In plasma VLDL is converted to low density lipoprotein (LDL)which in turn plays an important role in the development of atherosclerotic diseases; however,triglyceride (TG) rich VLDL1 has been shown to be more deleterious than cholesteryl ester (CE) rich VLDL2. There is evidence that the liver intracellular pool of CE and TG can regulate secretion of VLDL. To study the effect of CE pool on VLDLl and VLDL2 secretion, guinea pig liver was perfused with Krebs- Henseleit buffers containing lovastatin, progesterone and lovastatin plus progesterone. Perfusate pools of VLDL1 and VLDL2 were separated by cumulative flotation ultracentrifugation, confirmed by electron microscopy, and in each pool TG, CE and total lipid were measured. Progesterone had no significant effect on total lipid analysis in either VLDL1 or VLDL2 pools while lovastatin lowered the total lipid by 20% in VLDL1 and 41% in VLDL2 based on percent 90 minute point. Lovastatin decreased TG by 21% and CE by 20% in VLDL1 while it decreased TG by 39% and CE by 56% in VLDL2, based on percent 90 minute point slope change. On the other hand, while lovastatin plus progesterone lowered TG by 22% and CE by 23% in VLDL1, it lowers TG and CE by 39 and 64% in VLDL2, respectively. CE has an important role in the lipidation process and secretion of VLDL2 particles in normal guinea pig liver perfusion system.