Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis

Elena Galluccio, PierMarco Piatti, Lorena Citterio, P. C G Lucotti, Emanuela Setola, Laura Cassina, Matteo Oldani, Ivana Zavaroni, Emanuele Bosi, Antonio Colombo, Ottavio Alfieri, Giorgio Casari, Gerald M. Reaven, Lucilla D. Monti

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Little is known about the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms and the presence of insulin resistance and the early evolution of atherosclerosis in nondiabetic subjects with cardiovascular disease (CAD) and stent implantation. The present study was performed in an attempt to better understand whether metabolic, endothelial, and angiographic findings characteristic of subjects with cardiovascular disease and in-stent restenosis are related to NOS3 variants. This is a case-control study performed from 2002 to 2006. All subjects admitted to the study were recruited in the Nord-Centre of Italy, most from Milan and its surrounding towns. Measures of glucose tolerance, insulin sensitivity, markers of endothelial dysfunction, forearm vasodilation, and adipokine levels were determined and associated to the frequency of two single-nucleotide polymorphisms of NOS3, i.e., Glu 298Asp (rs1799983, G/T) and rs753482 (intron 18 A/C). A total of 747 subjects, not known to have diabetes, were evaluated: 333 subjects had asymptomatic CAD, 106 subjects had unstable angina and were evaluated for in-stent restenosis 6 mo after stent placement, and 308 were control subjects. The presence of TT and CC minor alleles was significantly greater in case groups compared with control subjects. At phenotypic level, subjects with the polymorphisms were characterized by hyperinsulinemia and reduced reactive hyperemia, whereas increased leptin and decreased adiponectin levels were present in subjects with restenosis in the presence of reduced minimal lumen diameter and length of stenosis almost doubled. Hyperinsulinemia, endothelial dysfunction, and a more atherogenic profile seem to be peculiar features of subjects with asymptomatic CAD and restenosis carrying NOS3 gene variants.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5
Publication statusPublished - May 2008


  • Coronary artery disease
  • NOS3 gene variants
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)


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