Involvement of extracellular-matrix-degrading metalloproteinases in rabbit aortic smooth-muscle cell proliferation.
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.
Southgate
K M
KM
Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Davies
M
M
Booth
R F
RF
Newby
A C
AC
D000818:Animals; D001011:Aorta / Q000166:cytology; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D017364:Collagenases / Q000032:analysis; D046508:Culture Techniques; D005109:Extracellular Matrix / Q000378:metabolism*; D005780:Gelatin / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D007163:Immunosorbent Techniques; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011817:Rabbits
D006877:Hydroxamic Acids; D009943:Organophosphorus Compounds; C078187:Ro 314724; C078189:Ro 317467; D005780:Gelatin; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1