Cellular And Molecular Mechanisms Associated With Salicylate Inhibition Of Intimal Hyperplasia Following Balloon Catheter-Induced Vascular Injury

Angioplasty followed by stein 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-kappa B. 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-kappa B 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.