Following treatment with bleomycin- and cisplatin-containing chemotherapy, 
testicular cancer patients frequently develop vascular complications, which may 
result from damage to endothelial cells. Understanding bleomycin- and 
cisplatin-induced endothelial alterations may help to develop strategies to 
prevent or reduce vascular toxicity. The effects of bleomycin and cisplatin on 
proliferation and apoptosis of the human dermal microvascular endothelial cell 
line HMEC-1 were determined. In addition, modulation of drug-induced 
cytotoxicity by the free radical scavenger amifostine, the low molecular weight 
heparin dalteparin, the iron-chelator dexrazoxane, the HMG-CoA reductase 
inhibitor rosuvastatin and the PPAR agonist troglitazone was tested. 
Furthermore, the effects of bleomycin and cisplatin on endothelial activation 
measured by the expression of the intercellular adhesion molecule-1 (ICAM-1) and 
on two main proteins involved in fibrinolysis, tissue-type plasminogen activator 
(tPA) and plasminogen activator inhibitor type 1 (PAI-1), were measured. 
Decreased endothelial cell survival induced by bleomycin and cisplatin coincided 
with the induction of apoptosis. Only troglitazone was able to protect the 
endothelial cells from both bleomycin- and cisplatin-induced cytotoxicity. At 
high concentrations, amifostine and dexrazoxane also protected HMEC-1 from 
drug-induced cytotoxicity. However, due to the required high (toxic) 
concentrations of both modulators no absolute cell survival benefit could be 
achieved. Both bleomycin and cisplatin induced up-regulation of ICAM-1, tPA and 
PAI-1. Summarizing, bleomycin and cisplatin induce alterations in the function 
of endothelial cells regarding proliferation, inflammation and fibrinolysis in 
vitro. Strategies aimed at these functions should be developed in order to 
ameliorate or prevent cytostatic agent-induced vascular damage.