Hirudin reduces tissue factor expression and attenuates graft arteriosclerosis in rat cardiac allografts
Research article published in Circulation (2000)
Abstract
BACKGROUND-Intravascular clotting has been implicated in the pathogenesis of cardiac allograft vasculopathy (CAV). We previously identified the expression of tissue factor (TF), the primary cellular initiator of blood coagulation, within the coronary intima, which was associated with neointimal thickening. In the present study, the effect of recombinant hirudin on CAV was assessed in Lewis to Fisher rat heterotopic cardiac allografts. METHODS AND RESULTS-Transplant recipients were randomized to a control group (n=10) and a hirudin-treated group (n=12; 2 mg. kg(-1). d(-1) SC). Histological evaluations of rejection, CAV, and TF staining were performed 120 days after transplantation. No significant differences were observed between the 2 groups with respect to the degree of rejection. Hirudin significantly (P<0.05) suppressed the development of CAV in the graft microvessels, but it was less effective in large coronary arteries. Graft intimal cells, isolated by laser-assisted cell picking, showed a marked upregulation of TF gene transcription, which was prevented by hirudin (P<0.01). As demonstrated by immunohistochemistry and quantitative analyses of TF mRNA levels by real-time polymerase chain reaction, hirudin treatment resulted in a significant reduction of TF protein and mRNA expression (P<0.001). CONCLUSIONS-Treatment with hirudin in this rat cardiac transplant model inhibited TF expression and decreased neointimal hyperplasia. These results suggest that TF inhibition by hirudin, in addition to its direct effect on thrombin, may attenuate the hypercoagulable state and prevent the development of CAV at least in restricted sites of the graft coronary vasculature.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Hirudin reduces tissue factor expression and attenuates graft arteriosclerosis in rat cardiac allografts.
Por qué esto importa para la hirudoterapia
Este estudio investigó el efecto de la hirudina recombinante sobre la vasculopatía del aloinjerto cardíaco (CAV) en un modelo de trasplante cardíaco heterotópico en rata, con receptores aleatorizados a un grupo control (n=10) o a un grupo de tratamiento con hirudina (n=12), evaluados a los 120 días postrasplante. La hirudina suprimió significativamente el desarrollo de CAV en los microvasos del injerto y redujo tanto la transcripción génica como la expresión proteica del factor tisular, aunque fue menos eficaz en las arterias coronarias de gran calibre y no alteró significativamente el grado de rechazo. El resumen enmarca el mecanismo en términos de inhibición del factor tisular y atenuación de un estado de hipercoagulabilidad. Sin embargo, estos resultados se limitan a un modelo en rata que emplea una formulación recombinante purificada, y el resumen no aborda las sanguijuelas, la hirudoterapia con el organismo completo ni la aplicación clínica en humanos.
Citación
Hirudin reduces tissue factor expression and attenuates graft arteriosclerosis in rat cardiac allografts
Holschermann H et al. · Circulation, 2000
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026