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Identification of genes involved in smooth muscle cell protein synthesis with increased expression in atheromathous plaques associated to neointimal hyperplasia after bare-metal stenting: GENESIS-R study

BACKGROUND: Coronary restenosis is a poorly understood phenomenon that remains a challenge even in the drug-eluting stent era. This study is aimed at identifying the genes involved in structural and functional protein synthesis of smooth muscle cells with increased expression in human atheromatous plaques associated to neointimal hyperplasia after bare-metal stent implantation. METHODS: Atheromatous plaques were obtained by directional atherectomy prior to stenting. Gene expression analysis was performed using the Affymetrix GeneChip system. Patients were submitted to intravascular ultrasound 6 months after the procedure for in-stent volumetric analysis. We evaluated the correlation between gene expression in atheromatous plaques and the percentage of in-stent intimal hyperplasia. RESULTS: Most patients were male (85.7%), with 60.2 ± 11.4 years of age, 35.7% were diabetic and the percentage of in-stent intimal hyperplasia was 29.9 ± 18.7%. There was no change in the percentage of in-stent intimal hyperplasia in patients with or without diabetes (29.5% vs. 30.7%; P = 0.89). There was no correlation between stent length and the percentage of in-stent intimal hyperplasia (r = -0.26; P = 0.26) or between stent diameter and the percentage of in-stent intimal hyperplasia (r = 0.14; P = 0.56). Eight genes related to smooth muscle cell structural and functional protein synthesis had a positive correlation with the percentage of in-stent intimal hyperplasia. CONCLUSIONS: De novo coronary lesions show increased expression of genes related to smooth muscle cell structural and functional protein synthesis associated to future significant in-stent neointimal hyperplasia, emerging as novel therapeutic targets.

Stents; Drug-eluting stents; Coronary restenosis; Gene expression; Atherectomy, coronary


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