Inducible cAMP early repressor inhibits growth of vascular smooth muscle cell

Objective - The role of inducible cAMP early repressor ( ICER), a transcriptional repressor, in the vascular remodeling process has not been determined. We examined whether ICER affects growth of vascular smooth muscle cells ( VSMCs). Methods and Results - Semi- quantitative RT- PCR and Western blot analysis showed that expression of ICER was increased in beraprost ( a prostaglandin I-2 analogue)- stimulated VSMCs in a time- and dose- dependent manner. The induction of ICER was inhibited by pretreatment with H89, a protein kinase A ( PKA) inhibitor, suggesting that PKA mediates the induction of ICER expression. Beraprost suppressed platelet- derived growth factor - induced thymidine incorporation in VSMCs, which was reversed by transfection of short interfering RNA for ICER, not by scramble RNA. Overexpression of ICER by an adenovirus vector attenuated neointimal formation ( intima/ media ratio) by 50% compared with overexpression of LacZ. The number of terminal deoxynucleotidyl transferase- mediated dUTP nick end- labeling - positive cells was increased and the number of Ki- 67 - positive cells was decreased in ICER- transduced artery. Conclusion - These results suggest that ICER induces apoptosis and inhibits proliferation of VSMCs, and plays a critical role in beraprost- mediated suppression of VSMC proliferation. ICER may be an important endogenous inhibitor of vascular proliferation.