Early inhibition of caspase-3 activity lessens the development of graft coronary artery disease
Related Experiment Video
Updated: Aug 17, 2026
Mouse Models for Graft Arteriosclerosis
Published on: May 14, 2013
Leora B Balsam1, G Kimia Mokhtari, Sophie Jones
1Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California 94305, USA. lbalsam@stanford.edu
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 microg 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.
Insights
Early inhibition of caspase-3, a key protein in cell death, reduces graft coronary artery disease (GCAD) development. This finding suggests caspase-3 inhibition as a potential strategy for preventing GCAD in heart transplant recipients.
Area of Science:
- Cardiovascular Research
- Transplantation Immunology
- Cellular Biology
Background:
- The role of apoptosis in graft coronary artery disease (GCAD) pathogenesis remains unclear.
- Previous studies indicated that Bcl-2 overexpression mitigates GCAD development.
- This study investigated the impact of caspase-3 inhibition on GCAD.
Purpose of the Study:
- To determine if early apoptosis inhibition using a caspase-3 inhibitor can reduce GCAD.
- To evaluate the efficacy of DEVD-CHO in preventing intimal proliferation and vascular occlusion in transplanted hearts.
Main Methods:
- Heterotopic heart transplantation was performed in four groups of rats.
- Donor and/or recipient hearts were pretreated with DEVD-CHO (caspase-3 inhibitor) or vehicle.
- Animals received cyclosporine to prevent acute rejection, and hearts were analyzed at 90 days post-transplant.
Main Results:
- DEVD-CHO treatment significantly reduced intimal proliferation compared to vehicle controls.
- A lower percentage of vessels exhibited high-grade occlusion (>50%) in inhibitor-treated animals.
- Early caspase-3 inhibition demonstrated a protective effect against GCAD development.
Conclusions:
- Early inhibition of caspase-3 activity using DEVD-CHO effectively lessens GCAD development.
- Caspase-3 inhibition presents a promising therapeutic strategy for preventing GCAD in clinical transplantation.
- Targeting apoptosis pathways may be crucial for long-term graft survival.
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