Temporally and Spatially Coordinated Expression of Cell Cycle Regulatory Factors After Angioplasty

Abstract

Intimal hyperplasia following angioplasty results in part from the migration and proliferation of vascular smooth muscle cells (VSMCs). However, the cell cycle regulatory networks underlying injury-induced VSMC proliferation are largely unknown. In the present study, we examined the kinetics of expression and activity of cell cycle regulatory factors after angioplasty in rat and human arteries. Cell lysates were prepared from uninjured rat carotid arteries and at different time points after balloon denudation. Marked induction of the proliferating cell nuclear antigen (PCNA), the G1/S cyclin-dependent kinase (cdk2), and its regulatory subunits (cyclin E and cyclin A) occurred between 1 and 2 days after angioplasty, was sustained up to 10 days after injury, and then declined. Induction of these factors correlated with increased cdk2-, cyclin E-, and cyclin A-dependent kinase activity, indicating the assembly of functional cdk2/cyclin E and cdk2/cyclin A holoenzymes in the injured arterial wall. Immunohisto...