L-arginine polymers inhibit the development of vein graft neointimal hyperplasia

Murray H. Kown, Atsushi Yamaguchi, Christina L. Jahncke, Douglas Miniati, Seiichiro Murata, Jurg Grunenfelder, Mark L. Koransky, Jonathan B. Rothbard, Robert C. Robbins

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Objective: We sought to determine whether L-arginine polymer treatment of vein grafts enhances vascular production of nitric oxide and inhibits the development of neointimal hyperplasia. Methods: External jugular veins of New Zealand White rabbits (n = 42) were harvested; treated intraluminally for 15 minutes with phosphate-buffered saline solution or L-arginine polymer 5, 7, or 9 at either 10 or 100 μmol/L; and then grafted into the contralateral carotid artery. Rabbits were killed after 28 days, and 5-μm sections of vessels were stained with hematoxylin and scored for intima/media ratio by using computerized morphometric analysis. Separate veins were treated in a similar fashion with biotinylated polymers and phosphate-buffered saline solution to assess for translocation efficiencies. Finally, vein segments pretreated with either phosphate-buffered saline solution or L-arginine polymers were cultured in Dulbecco's modified Eagle's medium containing lipopolysaccharide (100 μg/mL) and interferon μ (200 U/mL) for 48 hours before measuring nitric oxide levels by means of the Griess reaction. Results: Biotinylated L-arginine polymers demonstrated a dose- and length-dependent uptake into intimal and medial cells of treated vessels. Nitric oxide levels were significantly higher in vein segments treated with 100 μmol/L of L-arginine polymer 9 compared with control segments. Finally, the intima/media ratio also reflected both length- and concentration-dependent inhibition of neointimal hyperplasia. Intima/media ratio PBS R5 R7 R9 10 μmol/L 0.909±0.072 0.920±0.073 0.861±0.138 0.710±0.122 100 μmol/L 0.924±0.061 0.581±0.089* 0.529±0.093* PBS, Phosphate-buffered saline solution; R, L-arginine polymer. *P < .001 versus phosphate-buffered saline solution and L-arginine polymer 5 controls (Bonferroni-corrected value). Conclusions: Arginine polymers of sufficient length and concentration were effective in increasing nitric oxide levels and reducing neointimal hyperplasia in this vein graft model.

Original languageEnglish (US)
Pages (from-to)971-980
Number of pages10
JournalJournal of Thoracic and Cardiovascular Surgery
Volume121
Issue number5
DOIs
StatePublished - May 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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