Statin effect on apo A-I synthesis is related to its mode of action Inhibition by mevalonate Figure 106 If mevalonate is added to cells with statin-induced increased production of apo A-I, the increase in production is completely blocked and apo A-I levels return to normal. This confirms that the effect of statins is indirect and related to their known mechanism of action on the cholesterol synthesis pathway.

Statins and PPARa activators increase human apo A-I gene expression Figure 107 PPARa activation is achieved indirectly by statins, and directly by PPARa activators. The combination of statins and PPARa activators has a synergistic effect on apo A-I production.

Simvastatic acid reduces induced LPS MPP9 secretion Figure 108 The synergistic effect of statins and PPARa activators was explored in primary murine macrophages. Simvastatic acid reduces lipopolysaccharide-induced secretion of MPP9, as do PPARa activators but both in combination produce a synergistic effect.

Parietal vascular effects of statins (1) Endothelial cells Figure 109 The parietal vascular effects of some statins are also similar to the parietal vascular effects of PPARa agonists. This is particularly true with respect to decreased ET-1 production.

Parietal vascular effects of statins (2) Monocytes, macrophages Figure 110 Statins act on different factors of vascular inflammation. Indirect activation of PPARa may result in: reduced metalloprotease production; diminished production of some cytokines; decreased TF production.

PPARa activators act on the main factors involved in the onset of atherosclerosis Figure 111 PPARa activation plays a major role in modifying the main factors involved in the development of AS.