In vitro pharmacological inhibition of human vascular smooth muscle cell proliferation for the prevention of hemodialysis vascular access stenosis.
BACKGROUND
Vascular access for chronic hemodialysis often fails as a result of stenosis caused primarily by the proliferation of vascular smooth muscle cells (VSMC). Various drugs have been shown to inhibit the proliferation of VSMC under different conditions.


METHODS
In this study, we compared the inhibitory effect of ten drugs on the proliferation of human aortic smooth muscle cells (SMC) in culture. Quiescent cells were cultured in the presence of growth factors, fetal bovine serum and incremental concentrations of the test drug. Cell proliferation was assessed by the MTT reduction assay.


RESULTS
Aspirin, enalaprilat, heparin, hydroxyurea, indomethacin and tirofiban were ineffective. While dipyridamole, paclitaxel, tranilast and verapamil inhibited cell proliferation, the concentrations required were significantly higher than the clinical plasma levels achieved after systemic administration.


CONCLUSIONS
Local delivery of these drugs to the target site may therefore be a more effective and appropriate strategy for the prevention of hemodialysis vascular access stenosis.
Masaki
Takahisa
T
Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, Utah, USA. takahisa.masaki@hsc.utah.edu
Kamerath
Craig D
CD
Kim
Seung-Jung
SJ
Leypoldt
John K
JK
Mohammad
Syed F
SF
Cheung
Alfred K
AK
D000970:Antineoplastic Agents / Q000494:pharmacology; D001011:Aorta; D002408:Catheters, Indwelling / Q000009:adverse effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006801:Humans; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D006435:Renal Dialysis / Q000009:adverse effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000970:Antineoplastic Agents; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents