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.
MeSH Terms
Animals
Aorta/cytology
Blotting, Western
Cell Division/drug effects,physiology
Collagenases/analysis
Culture Techniques
Extracellular Matrix/metabolism
Gelatin/metabolism
Hydroxamic Acids/pharmacology
Immunosorbent Techniques
Matrix Metalloproteinase 1
Matrix Metalloproteinase 3
Metalloendopeptidases/analysis,antagonists & inhibitors,metabolism
Muscle, Smooth, Vascular/cytology
Organophosphorus Compounds/pharmacology
Rabbits
Chemicals
Hydroxamic Acids
Organophosphorus Compounds
Ro 314724
Ro 317467
Gelatin
Collagenases
Metalloendopeptidases
Matrix Metalloproteinase 3
Matrix Metalloproteinase 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Southgate K M
Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Davies M
Booth R F
Newby A C
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