Sphingolipids and Atherosclerosis

hen inhibitors of biochemical pathways are fed to experimental animals, the goals are to understand physiological or pathophysiological consequences of the inhibited pathway and possibly to obtain evidence for new therapeutic strategies for diseases affected by the pathway.In this issue of Circulation, Park et al 1 fed Apoe Ϫ/Ϫ mice a compound isolated from fungi, myriocin, that inhibits the rate-limiting enzyme in ceramide and sphingolipid biosynthesis, serine palmitoyl transferase (SPT).The study was founded on a series of previous observations that implicated sphingomyelin (SM) and ceramide in lipoprotein metabolism and atherosclerosis, including a study showing that plasma SM is an independent risk factor for coronary artery disease in humans. 2 The goal of the study by Park et al 1 was to test the effect of myriocin on plasma lipoprotein levels and atherogenesis in a well-defined animal model of atherosclerosis.The authors found that myriocin treatment in Apoe Ϫ/Ϫ mice was associated with a protective lipoprotein profilenamely, a decrease in ␤VLDL and LDL, an increase in HDL, and a reduction in atherosclerosis.