Abstract
We investigated the influence of two structurally unrelated inhibitors of matrix-degrading metalloproteinases, Ro 31-4724 and Ro 31-7467, on the primary proliferation of smooth-muscle cells from rabbit aortic explants. Both agents inhibited proliferation in a concentration-dependent manner, but did not affect cell viability. Smooth-muscle cells grown out from explants secreted 95 kDa and 72 kDa gelatinase enzymes that were also inhibited in a concentration-dependent manner by Ro 31-4724 and Ro 31-7467. Interstitial collagenase and stromelysin were not detected. We conclude that metalloproteinases are likely to be involved in the initiation of smooth-muscle proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aorta / cytology
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Blotting, Western
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Cell Division / drug effects
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Cell Division / physiology*
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Collagenases / analysis
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Culture Techniques
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Extracellular Matrix / metabolism*
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Gelatin / metabolism
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Hydroxamic Acids / pharmacology
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Immunosorbent Techniques
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Matrix Metalloproteinase 1
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Matrix Metalloproteinase 3
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Metalloendopeptidases / analysis
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Metalloendopeptidases / antagonists & inhibitors
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Metalloendopeptidases / metabolism*
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Muscle, Smooth, Vascular / cytology*
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Organophosphorus Compounds / pharmacology
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Rabbits
Substances
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Hydroxamic Acids
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Organophosphorus Compounds
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Ro 314724
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Ro 317467
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Gelatin
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Collagenases
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Metalloendopeptidases
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 1