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

The beta -lactone isolated from Fusarium termed L-659,699 is a potent speci fic inhibitor of the enzyme 3-hydroxi-3-methylglutaril coenzyme A (HMG-CoA) synthase. In cultures of smooth muscle cells (SMC) isolated from aortic-ar ch of control (C-SMC) and 5% of cholesterol diet (Ch-SMC) treated chicks, t he incorporation of (C-14)-acetate to lipids (cholesterol, triacylglyceride s and cholesterol ester) were greater in Ch-SMC cultures than in C-SMC and the presence of 0.05 muM L-659,699 for 2 h in the incubation medium decreas e the synthesis of cholesterol however the triacylglycerides synthesis incr ease. The effect of inhibitor is stronger in young cultures (3-4 steps) tha n in the older ones (11-12 steps). In young C-SMC and Ch-SMC cultures the i nhibition of cholesterol and triacylglycerides synthesis by L-659,699 was r eversal.