Genetic risk factors and restenosis after percutaneous coronary interventions

Restenosis is the major limitation of percutaneous coronary interventions. Depending on the form of intervention and patients' characteristics, 20 to 50% of the treated patients incur significant restenosis. Restenosis is caused by a complex and only partially understood cascade of events. Thrombus formation at the injury site, formation of the neointima as a result of the migration and proliferation of smooth muscle cells (SMC) and extracellular matrix production, as well as constrictive remodeling of the vessel wall contribute by a variable degree to restenosis. Restenosis is not a random event but it affects selectively a certain subset of patients. These patients have some peculiar characteristics that help to identify the presence of a higher risk for restenosis. Conventional patient-related factors account only for a relatively small portion of the predictive power, much more contribution comes from lesion and procedural characteristics. There is increasing evidence that inherited factors may explain at least part of the excessive risk for restenosis observed in certain patients. Evidence exists that gene polymorphisms may lead to quantitative or functional alterations of the respective gene products. Recent studies have also found significant associations between several polymorphic alleles encoding for proteins with a relevant role in the process of lumen renarrowing and restenosis after percutaneous coronary interventions. The best studied polymorphisms in this regard are those of the genes encoding for angiotensin-converting enzyme and platelet glycoprotein-IIIa. Completed or ongoing studies have focused on polymorphisms of genes encoding for proteins interfering with lipid metabolism, hemostasis, nitric oxide production, inflammatory mechanisms, SMC proliferation and matrix production. The results of this research will have considerable pathophysiological and therapeutical implications for the battle against restenosis.