Dipyridamole inhibits human mesangial cell proliferation.
BACKGROUND
Many glomerular diseases are associated with mesangial cell proliferation and the accumulation of extracellular matrix. At present, there are, however, few treatments which can inhibit these processes. The current study assessed the effects of the anti-platelet and putative anti-proliferative drug dipyridamole (DP) on the growth of human mesangial cells in vitro and their production of the extracellular matrix protein, fibronectin.


METHODS
Human mesangial cell proliferation, both intrinsic and stimulated by platelet-derived growth factor, was assessed using 3H-thymidine incorporation and an MTT proliferation assay. A sandwich enzyme-linked immunosorbent assay was used to study the effects of DP on fibronectin synthesis, again in cells stimulated by transforming growth factor beta 1 and in unstimulated cells.


RESULTS
At concentrations compatible with the serum levels found in subjects consuming standard dosages, DP significantly inhibited the growth of human mesangial cells in vitro in a dose-dependent fashion. DP also abrogated the mitogenic effects of platelet-derived growth factor. It had no significant effects on the synthesis of fibronectin by these cells (either spontaneous or induced by transforming growth factor beta 1). There was no evidence of cytotoxicity.


CONCLUSIONS
These data suggest that DP may have a therapeutic role in proliferative glomerulonephritis and possibly other diseases characterized by cell proliferation.
Hillis
G S
GS
Department of Medicine and Therapeutics, University of Aberdeen, UK.
Duthie
L A
LA
MacLeod
A M
AM
D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004176:Dipyridamole / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors
D005353:Fibronectins; D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D004176:Dipyridamole