title: The nitric oxide precursor L-arginine reduces expression of hyaluronan synthase in experimental vein bypass grafts.
abstract: BACKGROUND
  The success of vascular bypass procedures is limited by the development of intimal hyperplasia (IH). The nitric oxide (NO) precursor, L-arginine (L-ARG) significantly reduces IH in both arteries and experimental vein grafts; however, the precise mechanism has yet to be elucidated. Hyaluronan synthase-1 (HAS-1) is one of the two enzymes believed to be responsible for making hyaluronan, a key component extracellular matrix composition.
  
  
  OBJECTIVE
  To determine how L-ARG supplementation affects the gene expression of HAS-1 in experimental vein grafts.
  
  
  METHODS
  Thirty-four male New Zealand white rabbits were divided into three groups: control (no operation, regular chow and water, n = 4); L-ARG supplemented (n = 15); and no L-ARG (n = 15). The latter two groups underwent a right interposition carotid bypass using jugular vein. Vein grafts were harvested at 7, 14, and 21 days after surgery. Ribonuclease protection assays were performed using 32P-labeled riboprobes for HAS-1 and 18S rRNA as an internal control and expressed as a ratio (HAS-1/rRNA).
  
  
  RESULTS
  There was a significant rise in HAS-1 expression in the vein grafts 7 (1.57 +/- 0.5), 14 (0.7 +/- 0.2), and 21 days (2.82 +/- 0.7) after grafting compared to control (0.14 +/- 0.08) (P < 0.05). L-ARG-supplemented animals had a significant decrease in HAS-1 expression at 21 days (0.65 +/- 0.1) compared to nonsupplemented vein grafts (2.82 +/- 0.7) (P < 0.02).
  
  
  CONCLUSIONS
  These results demonstrate for the first time a significant rise in HAS expression in the early experimental vein grafts. Furthermore, L-ARG supplementation significantly diminishes the expression of HAS at 21 days. These results may represent a potential mechanism by which augmentation of the L-ARG/NO pathway inhibits IH in experimental vein grafts and may ultimately provide for improved therapeutic interventions in alleviating IH.
authors.affiliation: Hunter H. McGuire Veterans Administration Medical Center, Richmond, Virginia, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Dattilo
authors.forename: M P
authors.initials: MP
authors.lastname: Dattilo
authors.forename: J T
authors.initials: JT
authors.lastname: Crane
authors.forename: D R
authors.initials: DR
authors.lastname: Yager
authors.forename: R G
authors.initials: RG
authors.lastname: Makhoul
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D002339:Carotid Arteries / Q000601:surgery; D015870:Gene Expression / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000235:genetics*; D016695:Glycosyltransferases; D000076002:Hyaluronan Synthases; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D007527:Isoenzymes / Q000235:genetics*; D007601:Jugular Veins / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery*; D008297:Male; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D014166:Transferases; D014656:Vascular Surgical Procedures; D029867:Xenopus Proteins
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; D009569:Nitric Oxide; D001120:Arginine; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases