Abstract
Proliferation of acortic smooth muscle cells (SMC) is one of the key events in restenosis after percutaneous transluminal coronary angioplasty (PTCA). We studied the growth behavior of SMC after rat aortic injury, and the effect of polyamine synthesis inhibitors on the growth of SMC.3H-thymidine incorporation into SMC in aorta denuded with a balloon catheter started at 25 hours after injury, and maximal incorporation occurred 33 to 37 hours after injury. Transient increase in ODC activity was observed within 8 hours after injury. The polyamine level increased and were maximal at 48 hours after injury. Increased levels of spermidine continued until 7 days after injury. Intimal thickening started 7 days after injury and peaked at 21 days.Administration of α-difluoromethylornithine (DFMO), a specific inhibitor of ODC, prevented the enhancement of ODC activity stimulated by aortic injury. Combined administration of DFMO and methyglyoxal bis (guanylhydrazone) (MGBG), a specific inhibitor of S-adenosylmethionine decarboxylase (SAMDC), inhibited the increase in DNA synthesis as well as the polyamine level in the injured aorta, but had no effect on intimal thickening.
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