Endothelial cell response to hyperlipemia. Activation-dysfunction-injury, the protective role of simvastatin

Experiments on hypercholesterolemic rabbits and hamsters (HH) showed that hyperlipemia induces initial activation of endothelial cells (EC) expressed by modulation of constitutive functions: increased transcytosis of low-density lipoproteins (LDL) and enhanced synthesis of basal lamina. Accumulated LDL appears in the meshes of basal lamina as modified and reassembled lipoproteins (MRL) that, together with hyperlipemia, triggers EC dysfunction. This induces monocyte recruitment, adhesion, diapedesis and residence within the subendothelium where upon activation become macrophages, take up MRL and turn into foam cells. With time, EC overlaying atheroma alter their nonthrombogenic surface and become loaded with lipid droplets, resulting as marks of EC injury. Simvastatin administration to HH increased the antioxidant potential of the serum, diminished transcytosis of lipoproteins (Lp) and restored the endothelium-dependent relaxation.