ABSTRACT
A paradigm shift has taken place over the past decade with the emergence of stent angioplasty as a major therapeutic advance for treating coronary artery disease. Coronary stenting typically utilizes balloon expandable metallic meshwork stents (Figures 39.1A and 39.1B) that provide immediate relief to arteries obstructed by either progressive arteriosclerosis or thrombosis or both. A second wave of novel technology is now emerging in this field with the advent of drug eluting stents to prevent the development of in-stent restenosis (ISR). ISR is a complex disease process (see below) in which the angioplasty-injured artery develops a secondary obstructive injury response (Figure 39.1C). At this time laboratory investigations are actively exploring the next frontier for stent development, which will involve molecular therapy constructs configured on stents that will utilize either gene therapy vectors or cellular therapies with genetically engineered cells. The use of stents as delivery systems for molecular therapy constructs offers the greatest promise of all of the advances thus far, since it can enable not only therapies to address ISR, but treatment of the underlying vascular disease, and even downstream disease processes that may impact on individual patients. This chapter will approach the subject of gene delivery stents by reviewing the challenges posed by stent angioplasty and how they can be addressed with relevant candidate genes and delivery systems.
