Modulation of arterial smooth muscle cells from contractile to synthetic phenotype requires induction of ornithine decarboxylase activity and polyamine synthesis

The role of polyamines in modulating cultivated arterial smooth muscle cells from contractile to synthetic phenotype was studied by biochemical and electron microscopic methods. Ornithine decarboxylase (ODC), the first and overall rate-limiting enzyme in polyamine biosynthesis, showed no detectable activity in freshly isolated contractile cells, rose to a peak of activity after 2 days of culture, simultaneously with the most rapid phase of phenotypic modulation, and thereafter returned to a lower level of activity. The increase in ODC activity was accompanied by a gradual rise in the cellular concentrations of the polyamines putrescine, spermidine and spermine. The polyamine synthesis inhibitors α-difluoromethylornithine and methylglyoxal- bis(guanylhydrazone) prevented transition into synthetic phenotype as well as initiation of cell growth. The results indicate that polyamines play an important role in the control of smooth muscle phenotype and growth.