Contribution of endothelial injury and inflammation in early phase to vein graft failure: The causal factors impact on the development of intimal hyperplasia in murine models

Chi Nan Tseng, Eva Karlöf, Ya Ting Chang, Mariette Lengquist, Pierre Rotzius, Per Olof Berggren, Ulf Hedin, Einar E. Eriksson

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objectives: Autologous veins are preferred conduits in by-pass surgery. However, long-term results are hampered by limited patency due to intimal hyperplasia. Although mechanisms involved in development of intimal hyperplasia have been established, the role of inflammatory processes is still unclear. Here, we studied leukocyte recruitment and intimal hyperplasia in inferior vena cava grafts transferred to abdominal aorta in mice. Methods and Results: Several microscopic techniques were used to study endothelium denudation and regeneration and leukocyte recruitment on endothelium. Scanning electron microscopy demonstrated denudation of vein graft endothelium 7 days post-transfer and complete endothelial regeneration by 28 days. Examination of vein grafts transferred to mice transgenic for green fluorescent protein under Tie2 promoter in endothelial cells showed regeneration of graft endothelium from the adjacent aorta. Intravital microscopy revealed recruitment of leukocytes in vein grafts at 7 days in wild type mice, which had tapered off by 28 days. At 28 and 63 days there was significant development of intimal hyperplasia. In contrast; no injury, leukocyte recruitment nor intimal hyperplasia occurred in arterial grafts. Leukocyte recruitment was reduced in vein grafts in mice deficient in E- and P-selectin. In parallel, intimal hyperplasia was reduced in vein grafts in mice deficient in E- and P-selectin and in wild type mice receiving P-selectin/E-selectin function-blocking antibodies. Conclusion: The results show that early phase endothelial injury and inflammation are crucial processes in intimal hyperplasia in murine vein grafts. The data implicate endothelial selectins as targets for intervention of vein graft disease.

Original languageEnglish (US)
Article numbere98904
JournalPloS one
Volume9
Issue number6
DOIs
StatePublished - Jun 2 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Contribution of endothelial injury and inflammation in early phase to vein graft failure: The causal factors impact on the development of intimal hyperplasia in murine models'. Together they form a unique fingerprint.

  • Cite this