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La deficiencia del inhibidor de la vía del factor tisular promueve la aterosclerosis y la trombosis en ratones
R J Westrick1, P F Bodary, Z Xu
1Division of Cardiology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Circulation
|June 27, 2001
Resumen
La deficiencia del inhibidor de la vía del factor tisular (TFPI) exacerba la aterosclerosis y promueve la trombosis en ratones. Los niveles reducidos de TFPI aumentan la carga de la placa y aceleran la formación de coágulos, destacando el papel protector del TFPI.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- La hemostasis y la trombosis
- Investigación de la aterosclerosis Investigación de la aterosclerosis.
Sus antecedentes:
- El factor de tejido (TF) inicia la coagulación de la sangre después de la ruptura de la placa aterosclerótica.
- El inhibidor de la vía del factor tisular (TFPI, por sus siglas en inglés) antagoniza la actividad de TF, mitigando potencialmente la trombosis.
- El papel de la TFPI en el desarrollo de la aterosclerosis y las complicaciones trombóticas aún no se ha aclarado completamente.
Objetivo del estudio:
- Para investigar el impacto de la deficiencia heterocigótica de TFPI en la progresión de la aterosclerosis.
- Para evaluar el efecto de la deficiencia de TFPI en la trombosis en un modelo de ratón de aterosclerosis.
Principales métodos:
- Generación de ratones TFPI(+/-) /apoE(-/-) mediante el cruce de ratones heterocigotos TFPI y homocigotos apoE deficientes.
- Análisis exhaustivo de la carga aterosclerótica en todo el árbol vascular.
- Evaluación de la actividad TF de la placa y el tiempo hasta la trombosis oclusiva después de una lesión carotídea fotoquímica.
Principales resultados:
- La deficiencia de TFPI aumentó significativamente la carga aterosclerótica en la carótida y las arterias ilíacas comunes.
- Se observó una actividad elevada de TF dentro de las placas ateroscleróticas de ratones con deficiencia de TFPI.
- La deficiencia de TFPI redujo notablemente el tiempo hasta la trombosis oclusiva después de la lesión carotídea.
Conclusiones:
- TFPI confiere protección contra el desarrollo de la aterosclerosis.
- TFPI es un regulador crítico de la trombosis en el contexto de la aterosclerosis.
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