Inhibition of smooth muscle cell proliferation by an antisense oligodeoxynucleotide targeting the messenger RNA encoding proliferating cell nuclear antigen.

The process by which normally quiescent vascular smooth muscle cells (SMCs) change into proliferating cells, which express and respond to multiple growth factors, plays a major role in restenosis after coronary angioplasty. We are attempting to inhibit SMC proliferation by interventions that inhibit specific factors involved in signal transduction pathways leading to cell division. To date, all studies taking this approach have attempted to block the effects of mitogens acting on the cell surface. In contrast, we have focused on a strategy that bypasses cell surface-mediated events by directly inhibiting the expression of proliferating cell nuclear antigen (PCNA), an intranuclear protein that functions in a final common pathway shared by diverse mitogen-induced signals. In the present investigation, we determined whether antisense oligodeoxynucleotides (ODNs) complementary to the messenger RNA of PCNA will inhibit PCNA expression and thereby reduce SMC proliferation.