Amlodipine inhibits expression of matrix metalloproteinase-1 and its inhibitor in human vascular endothelial cells.
Matrix metalloproteinase-1 (MMP-1) may play an important role in the pathogenesis of atherosclerosis and atherosclerotic plaque rupture. We investigated the effect of the calcium channel blockers amlodipine and nifedipine on the expression of MMP-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in endothelial cells (ECs). MMP-1 and TIMP-1 levels in conditioned media of human vascular ECs were measured by enzyme-linked immunosorbent assay. Collagenolytic activity was determined by fluorescence-labeled collagen digestion. The addition of interleukin-1beta (IL-1beta) increased MMP-1 levels in the culture media of ECs. Amlodipine, but not nifedipine, significantly decreased MMP-1 levels in IL-1beta-stimulated ECs. TIMP-1 levels also were significantly increased by IL-1beta, and its expression was slightly decreased by amlodipine, not by nifedipine. Amlodipine significantly inhibited collagenolytic activity in the culture media of IL-1beta-stimulated ECs, whereas nifedipine showed no significant effect on the activity. Our findings revealed that amlodipine, but not nifedipine, inhibits IL-1beta-induced MMP-1 expression in human ECs.
Ikeda
U
U
Department of Cardiology, Jichi Medical School, Tochigi, Japan. uikeda@jichi.ac.jp
Hojo
Y
Y
Ueno
S
S
Arakawa
H
H
Shimada
K
K
D017311:Amlodipine / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000187:drug effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000187:drug effects*
D002121:Calcium Channel Blockers; D019715:Tissue Inhibitor of Metalloproteinase-1; D017311:Amlodipine; D003094:Collagen; D020781:Matrix Metalloproteinase 1