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Reduced progression of atherosclerosis in apolipoprotein E‐deficient mice treated with lacidipine is associated with a decreased susceptibility of low‐density lipoprotein to oxidation
Author(s) -
Cristofori Patrizia,
Crivellente Federica,
Campagnola Mario,
Pasini Anna Fratta,
Garbin Ulisse,
Rigoni Anna,
Tosetti Maria,
Turton John,
Faustinelli Ivo,
Cominacini Luciano
Publication year - 2004
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.0959-9673.2004.00375.x
Subject(s) - lacidipine , apolipoprotein b , endocrinology , medicine , lipid peroxidation , chemistry , antioxidant , lipoprotein , antagonist , low density lipoprotein , lipid profile , cholesterol , apolipoprotein e , pharmacology , oxidative stress , biochemistry , receptor , disease
Summary A study has been carried out in the apolipoprotein (apo) E‐deficient mouse to investigate the activity of lacidipine (a calcium antagonist with antioxidant properties) in inhibiting the development of atherosclerotic lesions; of particular interest were changes in the susceptibility of low‐density lipoproteins (LDL) to oxidation. Mice receiving a Western‐type diet to accelerate the development of atherosclerosis were treated orally with vehicle or lacidipine at 3 or 10 mg/kg/day for 8 weeks. Lacidipine treatment (at 3 or 10 mg/kg) had no effect on the plasma lipid profile. However, a significant ( P < 0.01) dose‐related reduction of 43 and 50% of the aortic lesion area in respect to vehicle‐treated mice was observed. Moreover, the resistance of mouse plasma LDL to undergo lipid peroxidation was significantly ( P < 0.01) increased in apo E‐deficient mice treated with lacidipine. The native LDL‐like particle, derived from apo E‐deficient mice treated with lacidipine, contained significantly lower concentrations of malonyldialdehyde than the vehicle‐treated control group ( P < 0.01). After exposure to human umbilical vein endothelial cells, LDL‐like particle vitamin E levels (expressed as area under the curve; AUC), were significantly higher ( P < 0.01) in both the 3 and 10 mg/kg lacidipine‐treated groups, in comparison with the vehicle‐treated control animals. We conclude that lacidipine reduced the extent of the atherosclerotic area in hypercholesterolaemic apo E‐deficient mice, and that this reduction may be associated with the capacity of the drug to decrease the susceptibility of LDL to oxidation.