He also demonstrated that intimal smooth muscle cells in atheroma have an immature phenotype determined by decreased expression of smooth muscle myosin heavy chain isoforms. This suggests that SMC in the fibrous cap have an immature phenotype. However, lipid lowering by diet promoted a more mature SMC in the fibrous cap as determined by increased expression of SM2. These results suggest that lipid lowering can stabilize the plaque by not only by reducing the number of macrophages but also by promoting a more mature SMC in the intima. Recently this group showed that dietary lipid lowering reduces tissue factor expression and activity by macrophages and SMC in rabbit atheroma.
Tissue factor is a potent contributor to acute coronary events.
After 4 months of the high cholesterol diet, lesional macrophages expressed tissue factor in the intima. However, after lipid lowering therapy tissue factor was nearly undetectable, associated with a reduced number of macrophages. These results suggest that lipid lowering can stabilize the plaque by decreasing proteolytic and prothrombotic macrophages. To understand the mechanisms of reduced number of macrophages in the lesion they first measured the level of ROS production using lucigenin chemiluminescence assay. Aortic rings from hypercholesterolemic rabbits elaborated high levels of ROS production, compared to normal aorta.