Effects of lacidipine on experimental models of atherosclerosis.
OBJECTIVE
To evaluate the effect of lacidipine on the major processes of atherogenesis.


METHODS
Cell-culture methods were used to study the effect of lacidipine. Low-density lipoprotein (LDL) receptor expression and cholesterol esterification were evaluated in human skin fibroblasts and in mouse peritoneal macrophages, respectively. The effect of lacidipine on cellular proliferation was tested on aortic myocytes cultured from rat aorta.


RESULTS
Lacidipine did not affect LDL receptor expression, but it inhibited the ability of acetyl LDL to stimulate cholesterol esterification in macrophages by more than 95%. The drug inhibited cellular proliferation in a dose-dependent manner. This antiproliferative effect was confirmed in human femoral artery myocytes. In accord with the inhibitory effect on cellular growth, preliminary in vivo studies suggest that lacidipine may reduce neointimal formation induced by perivascular manipulation of the carotid artery in hypercholesterolemic rabbit.


CONCLUSIONS
Our results indicate that lacidipine may be antiatherosclerotic through an effect on the major processes involved in atheroma formation.
Bernini
F
F
Institute of Pharmacological Sciences, University of Milan, Italy.
Corsini
A
A
Raiteri
M
M
Soma
M R
MR
Paoletti
R
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D004951:Esterification / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D002788:Cholesterol Esters; D004095:Dihydropyridines; D011973:Receptors, LDL; C060285:lacidipine