Regulating the Regulators: Transcription Factors as Targets for Attenuating Proliferative Arteriopathies

The use of percutaneous transluminal coronary angioplasty (PTCA) and stenting to treat coronary artery disease has increased exponentially in the past decade. However, the long term efficacy of PTCA is significantly limited by the high incidence of vascular restenosis observed in as many as 30% of patients undergoing this procedure. Likewise, coronary allograft vasculopathy remains the major cause of graft failure. The lack of effective pharmacological interventions in preclinical and clinical studies is indicative of our poor understanding of the molecular mechanisms underlying vascular proliferative diseases. A wave of gene transcription is induced as part of the vascular response to injury, which initiates and maintains the progression of vascular remodeling and the neointimal hyperplasia characteristic of this disease. Because gene transcription is tightly regulated by transcription factors, they make attractive targets for combating proliferative arteriopathies. In this review, we will examine the cellular and molecular biology of proliferative arteriopathy, as well as summarize transcription factors that show promise as targets to combat vascular proliferative diseases.