The reversal of the inhibition on lipids synthesis by L-659,699 in arterial smooth muscle cells cultures.

The beta-lactone isolated from Fusarium sp. termed L-659,699 is a potent specific inhibitor of the enzyme 3-hydroxi-3-methylglutaril coenzyme A (HMG-CoA) synthase. In cultures of smooth muscle cells (SMC) isolated from aortic-arch of control (C-SMC) and 5% of cholesterol diet (Ch-SMC) treated chicks, the incorporation of (14C)-acetate to lipids (cholesterol, triacylglycerides and cholesterol ester) were greater in Ch-SMC cultures than in C-SMC and the presence of 0.05 microM L-659,699 for 2 h in the incubation medium decrease the synthesis of cholesterol however the triacylglycerides synthesis increase. The effect of inhibitor is stronger in young cultures (3-4 steps) than in the older ones (11-12 steps). In young C-SMC and Ch-SMC cultures the inhibition of cholesterol and triacylglycerides synthesis by L-659,699 was reversal.