Cellular and Molecular Mechanisms Associated with Salicylate Inhibition of Intimal Hyperplasia Following Balloon Catheter-Induced Vascular Injury

Angioplasty followed by stent placement, bare or drug-eluting, proved to be a major step forward in the treatment of coronary and carotid artery disease. It was soon recognized that patients undergoing these procedures presented with restenosis within 6 months. The cause of these failures was the development of intimal hyperplasia. Aspirin, acetylsalicylic acid, soon became a focus of therapeutic intervention alone or in combination with other drugs due to its antiplatelet properties. When it was recognized that inflammation is a primary underlying factor in vascular disease, the use of aspirin was further encouraged. More recently, the anti-inflammatory proprieties of aspirin other than inhibition of cyclooxygenase activity have been described, namely, alterations in the expression and formation of proinflammatory molecules such as NF-κB. However, aspirin has gastrointestinal side effects and bleeding problems. Salicylates became the drug of interest, and more recently salsalate, the dimeric form of salicylic acid, is being recognized for similar anti-inflammatory actions as well as for lowering hyperglycemic glucose levels in type 2 diabetics without the deleterious side effects of aspirin. As revascularization procedures in type 2 diabetics have proven to produce a greater degree of intimal hyperplasia and, therefore, procedure failures, the effect of salsalate on the development of intimal hyperplasia in animals exhibiting symptoms of the metabolic syndrome was studied; the authors reported salsalate decreased intimal hyperplasia, increased eNOS expression, decreased NF-κB and VEGF expression. It is concluded in this chapter that clinical trials are indicated to define the effect of salsalate on the development of intimal hyperplasia and inflammation.