Cytotoxic effects of a recombinant chimeric toxin on rapidly proliferating vascular smooth muscle cells.

Restenosis after percutaneous transluminal coronary angioplasty is associated with activation of medial smooth muscle cells (SMCs); they proliferate, migrate to the subintima, and narrow the vessel lumen. Cancer cells often express more cell surface receptors than do normal cells. This has allowed tumor cells to be specifically targeted using cytotoxic agents. We have examined whether a similar concept can be applied to rapidly proliferating but nontransformed SMCs. Pseudomonas exotoxin (PE; MW, 66 kDa) is a potent toxin that kills cells by inhibiting protein synthesis; its toxicity is diminished when its cell recognition domain is deleted to produce a 40-kDa protein (PE40).