Different inhibitory effects of immunosuppressive drugs on human and rat aortic smooth muscle and endothelial cell proliferation stimulated by platelet-derived growth factor or endothelial cell growth factor.
BACKGROUND
Vascular smooth muscle cell hyperplasia with resulting luminal narrowing is the main histologic feature of accelerated arteriosclerosis seen after organ transplantation (transplant arteriosclerosis) and after balloon angioplasty (restenosis). It limits long-term allograft survival, as well as the success rate of angioplasty. At present, effective prophylactic and therapeutic strategies for these complications are still missing. Studies of in vivo models of accelerated arteriosclerosis induced by allogeneic or mechanical injury to the vasculature indicate that certain immunosuppressive drugs have inhibitory properties on smooth muscle cell hyperplasia.


METHODS
This study summarizes the inhibitory effects of different immunosuppressive drugs in vitro on the growth factor-induced proliferation of vascular smooth muscle cells and endothelial cells isolated from human and rat thoracic aortas.


RESULTS
The immunosuppressants rapamycin and mycophenolic acid were potent in inhibiting smooth muscle and endothelial cell proliferation. Cyclosporine demonstrated some inhibition of smooth muscle and endothelial cell proliferation, but the inhibitory concentration50 (IC50) values were just below toxicity levels. FK506 revealed a moderate inhibitory activity but, interestingly, only for human cells. High concentrations of leflunomide inhibited in our experiments only rat smooth muscle and endothelial cell proliferation. Methylprednisolone showed a gradual inhibition over a broad concentration interval of rat and human smooth muscle cells and of rat but not of human endothelial cells.


CONCLUSIONS
These data indicate that all of the established and new immunosuppressants tested have antiproliferative properties on vascular cells. Rapamycin was by far the most potent one. Therefore immunosuppressants, especiallyrapamycin and mycophenolic acid, may be used for prevention of accelerated arteriosclerosis.
Mohacsi
P J
PJ
Cardiology, University Hospital, Bern, Switzerland.
Tüller
D
D
Hulliger
B
B
Wijngaard
P L
PL
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000209:etiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D016228:Endothelial Growth Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D016377:Organ Transplantation / Q000009:adverse effects; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D051381:Rats
D016228:Endothelial Growth Factors; D007166:Immunosuppressive Agents; D010982:Platelet-Derived Growth Factor