title: Both T-786C and G894T polymorphism of endothelial nitric oxide synthase affect in-vitro endothelium-dependent relaxation of internal mammary artery rings from patients with coronary artery disease.
abstract: OBJECTIVE
  Polymorphisms of endothelial nitric oxide synthase (eNOS) gene in the promoter (T-786C) and exon 7 (G894T) have been suggested to attenuate endothelial function. As it is unknown whether these polymorphisms, on top of classical risk factors, further deteriorate endothelium-dependent vasomotion, we aimed to elucidate the impact of both polymorphisms on the ex-vivo vasomotor function of left internal mammary artery rings from patients with coronary artery disease (CAD) undergoing coronary bypass surgery (CABG).
  
  
  METHODS
  Mammary artery rings from 51 consecutive patients with CAD were obtained during elective CABG. Endothelium-dependent ring relaxation was measured in vitro in an organ chamber using acetylcholine (10 to 3 x 10 mol/l). Polymorphisms were determined by polymerase chain reaction restriction length polymorphism.
  
  
  RESULTS
  Thirty-three per cent of patients were positive for the T-786C polymorphism, 25% for the G894T polymorphism, and 18% carried mutated alleles in both loci. Maximal acetylcholine-induced ring relaxation was 46.7+/-3.2% in T-786C, 59.6+/-4.2% in G894T, and 66.7+/-7.4% in T-786C/G894T compared with 94.9+/-2.0% in wild-type subjects (P<0.05 versus T-786C, G894T, T-786C/G894T). Patients positive for an eNOS polymorphism with more than three cardiovascular risk factors displayed a further attenuation of acetylcholine-mediated relaxation (45+/-6 %) compared with having up to three risk factors (59+/-3%, P<0.05).
  
  
  CONCLUSIONS
  In patients with CAD, in-vitro assessed endothelium-dependent relaxation of mammary arteries was significantly impaired in those positive for the T-786C or the G894T eNOS polymorphism. These results suggest that the presence of either one of the eNOS polymorphisms deteriorated endothelium-dependent vasodilatory capacity of large conduit vessels on top of classical risk factors in patients with CAD.
authors.affiliation: Department of Internal Medicine/Cardiology, University of Leipzig, Heart Center, Leipzig, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
authors.forename: Sven
authors.initials: S
authors.lastname: Möbius-Winkler
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Nicolas
authors.initials: N
authors.lastname: Doll
authors.forename: Stephan
authors.initials: S
authors.lastname: Gielen
authors.forename: Jan F
authors.initials: JF
authors.lastname: Gummert
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Mohr
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
mesh_terms: D000368:Aged; D000483:Alleles; D003327:Coronary Disease / Q000235:genetics / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000502:physiology*; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014664:Vasodilation / Q000502:physiology*
chemical_list: D052250:Nitric Oxide Synthase Type III