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 journalArticlepeer-review

11 Scopus citations

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Fingerprint Dive into the research topics of 'Early inhibition of caspase-3 activity lessens the development of graft coronary artery disease'. Together they form a unique fingerprint.

Cite this