Vascular smooth muscle cell proliferation in SHR and WKY rats: evidence for specific differences in growth inhibitory regulatory mechanisms.
1. This study examined and compared the actions of transforming growth factor-beta 1 (TGF-beta 1), heparin, dexamethasone and interferon-gamma on platelet-derived growth factor-BB (PDGF-BB)-stimulated proliferation of vascular smooth muscle cells (VSMC) from normotensive, Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Heparin, dexamethasone and interferon-gamma all inhibited VSMC proliferation stimulated by PDGF-BB in both SHR and WKY rats. There was no difference (P > 0.05) in their inhibitory effects, which varied between 40 and 85% for the different agents. 3. Similarly, TGF-beta 1 inhibited PDGF-BB-stimulated VSMC proliferation in WKY rats by approximately 50%. In contrast, TGF-beta 1 potentiated growth factor action on cell proliferation in the SHR by approximately 40%. 4. Specific TGF-beta 1-stimulated regulatory mechanisms involved in the inhibition of proliferation are absent in SHR and this defect may contribute to the vascular hypertrophy which is apparent in genetic hypertension.
Agrotis
A
A
Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia.
Bray
P J
PJ
Saltis
J
J
Bobik
A
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006973:Hypertension / Q000473:pathology*; D007371:Interferon-gamma / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D003907:Dexamethasone; D007371:Interferon-gamma; D006493:Heparin