Data di Pubblicazione:
2001
Citazione:
Lalsoacidipine modulates the secretion of matrix metalloproteinase-9 by human macrophages / S. Bellosta, M. Canavesi, E. Favari, L. Cominacini, G. Gaviraghi, R. Fumagalli, R. Paoletti, F. Bernini. - In: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. - ISSN 0022-3565. - 296:3(2001), pp. 736-743.
Abstract:
Activated macrophages within the arterial wall secrete matrixdegrading
metalloproteinases (MMPs) that weaken the atherosclerotic plaque and contribute to its fissuration. Preclinical
studies have shown that calcium antagonists may reduce
atherogenesis in the arterial wall. In the present study we evaluated
the effect of lacidipine on 92-kDa gelatinase B (MMP-9)
expression in human macrophages in cultures. Cells were
treated for 24 h with lacidipine and the conditioned media were
analyzed. Lacidipine (1–20 mM) significantly reduced, in a dosedependent manner, MMP-9 potential gelatinolytic capacity up to 50%. When MMP-9 expression was stimulated by treatment with phorbol esters or tumor necrosis factor-a, lacidipine was
able to inhibit this enhanced gelatinolytic capacity up to 50 and
60%, respectively. Western blot analysis and enzyme-linked
immunosorbent assay showed a reduction of MMP-9 protein
actually released by cells. The addition of lacidipine in the
incubation media determined no significant variation in Ca21
concentration. The drug did not affect MMP-9 mRNA levels, but
it effectively reduced the amount of both active and total free
MMP-9 secreted by human macrophages. Lacidipine reduced
also the secretion of the tissue inhibitor of metalloproteinase-1
(TIMP-1); however we observed an overall reduction of the
gelatinolytic activity of the cells. Finally, peritoneal macrophages,
obtained from mice treated with lacidipine, showed a
reduced secretion of MMP-9. Together, our data indicate that
lacidipine may potentially exert an antiatherosclerotic activity
by modulating the secretion of MMP-9 by macrophages. This,
in addition to the previously demonstrated inhibition of cholesterol
esterification, may contribute to increase plaque stability.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
S. Bellosta, M. Canavesi, E. Favari, L. Cominacini, G. Gaviraghi, R. Fumagalli, R. Paoletti, F. Bernini
Link alla scheda completa: