Captopril suppresses Post-transplantation angiogenic activity in rat allograft coronary vessels

Susan E. Crawford, Constantine Mavroudis, Carl L. Backer, Xuemei Huang, Yan Mu, Olga V. Volpert, Veronica Stellmach, Elfriede Pahl, Lijun Huang

Research output: Contribution to journalArticle

Abstract

Background The development of transplant coronary artery disease is associated with neovascularization in the thickened neointima. We previously reported that captopril inhibits neointimal proliferation in a rat allograft model. We postulated that angiogenic inducers are upregulated post-transplantation and captopril ameliorates transplant coronary artery disease by suppressing the angiogenic activity of coronaries. Methods Animals received no treatment or captopril (50 mg/kg/day). Allograft hearts were analyzed at post-transplantation Days 0, 14, and 21 and angiogenic inducer, plasma platelet-activating factor, determined. The conditioned media from coronaries and myocardium were tested for vascular endothelial growth factor, thrombospondin-1 and angiogenic activity using an endothelial migration assay and rat corneal neovascularization assay. Results The captopril-treated group had reduced plasma platelet-activating factor and coronary media revealed earlier upregulation of thrombospondin-1 secretion, diminished vascular endothelial growth factor and no angiogenic activity. At Day 0, the coronary and myocardial conditioned medium had inhibitory activity due to thrombospondin-1, and circulating levels of platelet-activating factor were negligible. By 21 days post-transplantation, plasma platelet-activating factor was elevated and the conditioned medium from untreated coronaries had significantly higher angiogenic activity due to increased vascular endothelial growth factor whereas the myocardium remained non-angiogenic. Conclusions After transplantation, coronary vessels switch to an angiogenic phenotype and vascular endothelial growth factor contributes to the high angiogenic activity, possibly exacerbated by high circulating levels of platelet-activating factor. The ability of captopril to modulate angiogenic mediators and maintain the allograft coronary to its normal anti-angiogenic phenotype may be one mechanism by which it suppresses transplant coronary artery disease.

Original languageEnglish (US)
Pages (from-to)666-673
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume23
Issue number6
DOIs
StatePublished - Jun 1 2004
Externally publishedYes

ASJC Scopus subject areas

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

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    Crawford, S. E., Mavroudis, C., Backer, C. L., Huang, X., Mu, Y., Volpert, O. V., Stellmach, V., Pahl, E., & Huang, L. (2004). Captopril suppresses Post-transplantation angiogenic activity in rat allograft coronary vessels. Journal of Heart and Lung Transplantation, 23(6), 666-673. https://doi.org/10.1016/j.healun.2003.07.010