Genomic alterations associated to restenosis after coronary angioplasty with stent

Abstract

Currently, the most widely used procedure in the treatment of coronary lesions is angioplasty with stent-implantation procedure. However, despite the breakthroughs and developments associated with this procedure, acute and chronic complications can emerge, being restenosis the major limiting factor for this therapy. It is known that restenosis is a multifactorial and multigenic process, whose genesis is related to remodeling of the vessel, the local formation of thrombus, the proliferation of the neointimal layer and the excessive production of extracellular matrix. Therefore, the present investigation aims to identify molecular biomarkers related to restenosis, particularly the mechanisms involved in coronary endothelial hyperplasia. The specific objectives of the study are: to assess the relationship between gene polymorphisms (metalloproteinase genes) and restenosis, and to evaluate the level of oxidative DNA damage and gene expression profile in peripheral blood leukocytes of patients with stent implantation (with and without restenosis). Using in vitro systems the objectives are: to evaluate the gene expression profile, cell cycle and gene regulation mechanisms (DNA methylation and miRNA) in smooth muscle and endothelial cells exposed to chemical and mechanical stress. Gene polymorphisms will be determined using real-time PCR and gene expression profile using PCR array technology; oxidative DNA damage will be determined using the comet assay; cell cycle and apoptosis will be evaluated by flow cytometry. (AU)