DIPYRIDAMOLE INHIBITS HUMAN MESANGIAL CELL-PROLIFERATION

Background: Many glomerular diseases are associated with mesangial cel l proliferation and the accumulation of extracellular matrix. At prese nt, there are, however, few treatments which can inhibit these process es. The current study assessed the effects of the anti-platelet and pu tative anti-proliferative drug dipyridamole (DP) on the growth of huma n mesangial cells in vitro and their production of the extracellular m atrix protein, fibronectin. Methods: Human mesangial cell proliferatio n, both intrinsic and stimulated by platelet-derived growth factor, wa s assessed using H-3-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. Result s: At concentrations compatible with the serum levels found in subject s consuming standard dosages, DP significantly inhibited the growth of human mesangial cells in vitro in a dose-dependent fashion. DP also a brogated the mitogenic effects of platelet-derived growth factor. It h ad no significant effects on the synthesis of fibronectin by these cel ls (either spontaneous or induced by transforming growth factor beta 1 ). There was no evidence of cytotoxicity. Conclusion: These data sugge st that DP may have a therapeutic role in proliferative glomerulonephr itis and possibly other diseases characterized by cell proliferation.