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.
Simionescu
Maya
M
Institute of Cellular Biology and Pathology Nicolae Simionescu, 8, B.P. Hasdeu Street, Bucharest, 79691, Romania. simionescum@simionescu.instcellbiopath.ro
Stancu
Camelia
C
Costache
Gabriela
G
Sima
Anca
A
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D004041:Dietary Fats / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*
D004041:Dietary Fats; D019821:Simvastatin