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Carbon Monoxide Rescues Heme Oxygenase-1-Deficient Mice from Arterial Thrombosis in Allogeneic Aortic Transplantation
- Source :
- The American Journal of Pathology. 175:422-429
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Heme oxygenase-1 (HO-1) catalyzes the conversion of heme into carbon monoxide (CO), iron, and biliverdin. In preliminary studies, we observed that the absence of HO-1 in aortic allograft recipients resulted in 100% mortality within 4 days due to arterial thrombosis. In contrast, recipients normally expressing HO-1 showed 100% graft patency and survival for more than 56 days. Abdominal aortic transplants were performed using Balb/cJ mice as donors and either HO-1(+/+) or HO-1(-/-) (C57BL/6xFVB) mice as recipients. Light and electron microscopy revealed extensive platelet-rich thrombi along the entire length of the graft in HO-1(-/-) recipients at 24 hours. Treatment of recipients with CORM-2, a CO-releasing molecule (10 mg/kg of body weight intravenously), 1 hour prior and 1, 3, and 6 days after transplantation, significantly improved survival (62% at56 days, P0.001) compared with HO-1(-/-) recipients treated with inactive CORM-2 (median survival 1 day). Histological analyses revealed that CO treatment markedly reduced platelet aggregation within the graft. Adoptive transfer of wild-type platelets to HO-1(-/-) recipients also conferred protection and increased survival. Aortic transplants from either HO-1(-/-) or HO-1(+/+) C57BL/6 donors into HO-1(+/+) (Balb/cJ) mice did not develop arterial thrombosis, surviving more than 56 days. These studies demonstrate an important role for systemic HO-1/CO for protection against vascular arterial thrombosis in murine aortic allotransplantation.
- Subjects :
- Pathology
medicine.medical_specialty
medicine.medical_treatment
Blotting, Western
Pathology and Forensic Medicine
Andrology
Mice
Microscopy, Electron, Transmission
medicine.artery
Animals
Transplantation, Homologous
Medicine
Platelet
Aorta
Carbon Monoxide
business.industry
Graft Survival
Thrombosis
Organ Transplantation
medicine.disease
Heme oxygenase
Transplantation
medicine.anatomical_structure
Circulatory system
business
Heme Oxygenase-1
Regular Articles
Allotransplantation
Artery
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 175
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....cc59b62c70eaf14ba5dc0f4cf5440bd8