Early inhibition of caspase-3 activity lessens the development of graft coronary artery disease

Leora B. Balsam, G. Kimia Mokhtari, Sophie Jones, Shannon Peterson, E. Grant Hoyt, Theo Kofidis, Masashi Tanaka, David T Cooke, Robert C. Robbins

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: The role of apoptosis in the development of graft coronary artery disease (GCAD) is poorly understood. We have previously shown that early overexpression of the anti-apoptotic protein Bcl-2 lessens the development of GCAD. We hypothesized that early inhibition of apoptosis with a caspase-3 inhibitor would also lessen the development of GCAD. Methods: Heterotopic heart transplantation was performed in 4 groups of rats. Donor hearts were pretreated with 50 μg DEVD-CHO, a cell-permeable caspase-3 inhibitor, or vehicle. Recipient animals were pretreated with 1.7 mg/kg intraperitoneal DEVD-CHO or vehicle. Animals were treated with 7.5 mg/kg/d cyclosporine for 10 days to prevent acute rejection. On post-operative day 90, the animals were sacrificed and the transplanted hearts were assessed morphometrically for evidence of GCAD. Results: At 90 days, intimal proliferation was significantly higher in vehicle treated animals than in inhibitor treated animals. Moreover, the percentage of vessels with high-grade occlusion (>50%) was also lower in inhibitor treated animals. Conclusions: Early inhibition of caspase-3 activity with cell-permeable DEVD-CHO lessens the development of GCAD. Caspase-3 inhibition may be a useful strategy for prevention of GCAD in clinical transplantation.

Original languageEnglish (US)
Pages (from-to)827-832
Number of pages6
JournalJournal of Heart and Lung Transplantation
Volume24
Issue number7
DOIs
StatePublished - Jul 2005
Externally publishedYes

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Caspase 3
Coronary Artery Disease
Transplants
Caspase Inhibitors
Heterotopic Transplantation
Tunica Intima
Apoptosis
Apoptosis Regulatory Proteins
CHO Cells
Heart Transplantation
Cyclosporine
Transplantation
aspartyl-glutamyl-valyl-aspartal

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Cite this

Balsam, L. B., Mokhtari, G. K., Jones, S., Peterson, S., Hoyt, E. G., Kofidis, T., ... Robbins, R. C. (2005). Early inhibition of caspase-3 activity lessens the development of graft coronary artery disease. Journal of Heart and Lung Transplantation, 24(7), 827-832. https://doi.org/10.1016/j.healun.2004.05.015

Early inhibition of caspase-3 activity lessens the development of graft coronary artery disease. / Balsam, Leora B.; Mokhtari, G. Kimia; Jones, Sophie; Peterson, Shannon; Hoyt, E. Grant; Kofidis, Theo; Tanaka, Masashi; Cooke, David T; Robbins, Robert C.

In: Journal of Heart and Lung Transplantation, Vol. 24, No. 7, 07.2005, p. 827-832.

Research output: Contribution to journalArticle

Balsam, LB, Mokhtari, GK, Jones, S, Peterson, S, Hoyt, EG, Kofidis, T, Tanaka, M, Cooke, DT & Robbins, RC 2005, 'Early inhibition of caspase-3 activity lessens the development of graft coronary artery disease', Journal of Heart and Lung Transplantation, vol. 24, no. 7, pp. 827-832. https://doi.org/10.1016/j.healun.2004.05.015
Balsam, Leora B. ; Mokhtari, G. Kimia ; Jones, Sophie ; Peterson, Shannon ; Hoyt, E. Grant ; Kofidis, Theo ; Tanaka, Masashi ; Cooke, David T ; Robbins, Robert C. / Early inhibition of caspase-3 activity lessens the development of graft coronary artery disease. In: Journal of Heart and Lung Transplantation. 2005 ; Vol. 24, No. 7. pp. 827-832.
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