Genomics of In-Stent Restenosis

Inflammation is a key component of atherosclerosis. Abundant preclinical data support the hypothesis that atherosclerosis is a chronic inflammatory disorder.1,2 Indeed, clinical trial data now provide evidence that inflammation, as reflected in serum markers such as C-reactive protein and interleukin-6, is a strong risk factor for the development and progression of atherosclerosis.3,4 The role of genetic factors in determining a predisposition or susceptibility to inflammation that exacerbates atherosclerosis is not fully known.Article p 2417 In-stent restenosis occurs after the deployment of an intravascular stent within an atherosclerotic lesion. The fibroproliferative response to this vascular “injury” typically develops within the first 9 months postprocedure. The response to injury follows a continuum in human arteries; some degree of cell proliferation occurs in all patients and can be thought of as a wound-healing process. In some individuals, however, the wound healing becomes excessive, leading to exuberant vascular smooth muscle cell growth and extracellular matrix synthesis, and encroachment on the arterial lumen, and resulting in a recurrence of clinical symptoms. Molecular and genetic studies suggest that cell cycle proteins, growth factors, and inflammatory cytokines regulate this process.5 Drug-eluting stents have dramatically reduced the prevalence of in-stent restenosis because of the local treatment of the fibroproliferation with 2 drugs, sirolimus and paclitaxel, which have antiproliferative and antiinflammatory properties.6,7 What is not known, however, is whether there is a genetic susceptibility that determines a patient’s response to stent deployment …