Effects of human endothelial gene polymorphisms on cellular responses to hyperglycaemia: Role of NOS3 (Glu298Asp) and ACE (I/D) polymorphisms

Mandar S. Joshi, Suvara Wattanapitayakul, Brandon L. Schanbacher, John A. Bauer

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The functional relevance of NOS3 and ACE genetic variations to endothelial cell function is largely unstudied. Here we tested the functional relevance of the NOS3 (Glu298Asp) polymorphism and ACE (I/D) polymorphism in endothelial cells in vitro. Our hypothesis was that these genetic polymorphisms alter endothelial cell sensitivity to glucose and 3-nitrotyrosine (3NT). Genotyped HUVECs were incubated with glucose, free 3NT or a combination of these two toxicants. Significant differences in glucose-induced cell death and free 3NT-induced cell death were observed among the NOS3 genotypes. Combined glucose/3NT caused increased toxicity among the NOS3 genotypes. No differences were observed among the ACE genotypes in their responses to glucose/3NT. These data demonstrate that the NOS3 genotype may be an important predictor of, or be mechanistically involved in, endothelial vulnerability, whereas the ACE I/D genotype is apparently less important. Thus this NOS3 genetic variation may play a role in vulnerability to endothelium-dependent diabetic vascular complications.

Original languageEnglish
Pages (from-to)276-283
Number of pages8
JournalDiabetes and Vascular Disease Research
Volume8
Issue number4
DOIs
StatePublished - Oct 2011

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health [Grant numbers HL63067 and DK55053; PI: JAB] and the Victorian Government’s Operational Infrastructure Support Program.

Keywords

  • angiotensin converting enzyme (ACE)
  • diabetes
  • endothelial nitric oxide synthase (NOS3)
  • genetic polymorphisms
  • vascular complications

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

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