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Captopril suppresses post-transplantation angiogenic activity in rat allograft coronary vessels.

Publication ,  Journal Article
Crawford, SE; Mavroudis, C; Backer, CL; Huang, X; Mu, Y; Volpert, OV; Stellmach, V; Pahl, E; Huang, L
Published in: J Heart Lung Transplant
June 2004

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.

Duke Scholars

Published In

J Heart Lung Transplant

DOI

ISSN

1053-2498

Publication Date

June 2004

Volume

23

Issue

6

Start / End Page

666 / 673

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Surgery
  • Rats, Inbred Lew
  • Rats, Inbred F344
  • Rats
  • Platelet Activating Factor
  • Neovascularization, Physiologic
  • Male
  • Heart Transplantation
  • Endothelial Cells
 

Citation

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Crawford, S. E., Mavroudis, C., Backer, C. L., Huang, X., Mu, Y., Volpert, O. V., … Huang, L. (2004). Captopril suppresses post-transplantation angiogenic activity in rat allograft coronary vessels. J Heart Lung Transplant, 23(6), 666–673. https://doi.org/10.1016/j.healun.2003.07.010
Crawford, Susan E., Constantine Mavroudis, Carl L. Backer, Xuemei Huang, Yan Mu, Olga V. Volpert, Veronica Stellmach, Elfriede Pahl, and Lijun Huang. “Captopril suppresses post-transplantation angiogenic activity in rat allograft coronary vessels.J Heart Lung Transplant 23, no. 6 (June 2004): 666–73. https://doi.org/10.1016/j.healun.2003.07.010.
Crawford SE, Mavroudis C, Backer CL, Huang X, Mu Y, Volpert OV, et al. Captopril suppresses post-transplantation angiogenic activity in rat allograft coronary vessels. J Heart Lung Transplant. 2004 Jun;23(6):666–73.
Crawford, Susan E., et al. “Captopril suppresses post-transplantation angiogenic activity in rat allograft coronary vessels.J Heart Lung Transplant, vol. 23, no. 6, June 2004, pp. 666–73. Pubmed, doi:10.1016/j.healun.2003.07.010.
Crawford SE, Mavroudis C, Backer CL, Huang X, Mu Y, Volpert OV, Stellmach V, Pahl E, Huang L. Captopril suppresses post-transplantation angiogenic activity in rat allograft coronary vessels. J Heart Lung Transplant. 2004 Jun;23(6):666–673.
Journal cover image

Published In

J Heart Lung Transplant

DOI

ISSN

1053-2498

Publication Date

June 2004

Volume

23

Issue

6

Start / End Page

666 / 673

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor A
  • Surgery
  • Rats, Inbred Lew
  • Rats, Inbred F344
  • Rats
  • Platelet Activating Factor
  • Neovascularization, Physiologic
  • Male
  • Heart Transplantation
  • Endothelial Cells