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

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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
Volume294
Issue number5
DOIs
Publication statusPublished - May 2008

Fingerprint

Stents
Nitric Oxide Synthase Type III
Adiponectin
Hyperinsulinism
Leptin
Polymorphism
Cardiovascular Diseases
Asymptomatic Diseases
Insulin Resistance
Genes
Insulin
Adipokines
Unstable Angina
Hyperemia
Medical problems
Forearm
Vasodilation
Introns
Italy
Single Nucleotide Polymorphism

Keywords

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

ASJC Scopus subject areas

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

Cite this

Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis. / Galluccio, Elena; Piatti, PierMarco; Citterio, Lorena; Lucotti, P. C G; Setola, Emanuela; Cassina, Laura; Oldani, Matteo; Zavaroni, Ivana; Bosi, Emanuele; Colombo, Antonio; Alfieri, Ottavio; Casari, Giorgio; Reaven, Gerald M.; Monti, Lucilla D.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 294, No. 5, 05.2008.

Research output: Contribution to journalArticle

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AU - Lucotti, P. C G

AU - Setola, Emanuela

AU - Cassina, Laura

AU - Oldani, Matteo

AU - Zavaroni, Ivana

AU - Bosi, Emanuele

AU - Colombo, Antonio

AU - Alfieri, Ottavio

AU - Casari, Giorgio

AU - Reaven, Gerald M.

AU - Monti, Lucilla D.

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