In vitro inhibitory effect of lercanidipine on cholesterol accumulation and matrix metalloproteinases secretion by macrophages
Articolo
Data di Pubblicazione:
2004
Citazione:
In vitro inhibitory effect of lercanidipine on cholesterol accumulation and matrix metalloproteinases secretion by macrophages / M. Canavesi, N. Baldini, A. Leonardi, G. Sironi, S. Bellosta, F. Bernini. - In: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. - ISSN 0160-2446. - 44:4(2004 Oct), pp. 416-422. [10.1097/01.fjc.0000139448.56713.3d]
Abstract:
Plaque rupture and thromboembolism play a major role in atherosclerotic acute syndrome. Experimental studies have demonstrated the potential direct anti-atherosclerotic effects of calcium antagonists. We investigated the in vitro effect of lercanidipine (REC 15/2375), a third-generation, highly lipophilic calcium antagonist on cholesterol metabolism and matrix metalloproteinases secretion in
macrophages, two functions that predispose plaques to rupture. Lercanidipine (10−6–10−5 M) inhibited cholesterol esterification in macrophagesand reduced cellular free and esterified cholesterol accumulation from acetylated LDL (63%, 62% of control P < 0.05, respectively). In addition, lercanidipine inhibited the release of metalloproteinases in the extracellular medium (50% and 95% inhibition at 10−5 M for MMP-9 and MMP-2, respectively). Experiments performed with lercanidipine enantiomers or other dihydropyridine derivatives, endowed with different lipophilicity and affinity for calcium channels, indicated that the above effects could be related to the lipophilic, but not to the calcium channel blocking properties of these molecules. When cells, after exposure to the drug, were allowed to
equilibrate, lercanidipine inhibitory action could be observed at initial concentrations as low as 10−9 M, which is the actual concentration range observed in plasma in clinical settings. In conclusion, our
data indicate that lercanidipine may exert potent anti-atherosclerotic effects by inhibiting macrophage functions involved in plaque stability.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
atherosclerosis ; calcium antagonists ; macrophages ; cholesterol esterification ; metalloproteinases
Elenco autori:
M. Canavesi, N. Baldini, A. Leonardi, G. Sironi, S. Bellosta, F. Bernini
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