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La simvastatina mejora la función perturbada de la barrera endotelial.

G P van Nieuw Amerongen1, M A Vermeer, P Nègre-Aminou

  • 1Gaubius Laboratory TNO-PG, Leiden, The Netherlands.

Circulation
|January 11, 2000
PubMed
Resumen

La simvastatina mejora la función de la barrera endotelial, reduciendo la fuga vascular y potencialmente contribuyendo a la reducción de eventos cardiovasculares más allá de la reducción de lípidos. Este estudio demuestra que la simvastatina es

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Área de la Ciencia:

  • Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular
  • Biología endotelial Biología endotelial.
  • Farmacología Farmacología.

Sus antecedentes:

  • Las estatinas (inhibidores de la reductasa de la coenzima A 3-hidroxi-3-metilglutarilo) reducen los eventos coronarios agudos.
  • Los beneficios de las estatinas se extienden más allá de la reducción de lípidos, lo que sugiere otros mecanismos.
  • La mejora de la función endotelial puede desempeñar un papel en los efectos cardioprotectores de las estatinas.

Objetivo del estudio:

  • Para investigar el efecto de la simvastatina en la función de la barrera endotelial.
  • Para determinar si la simvastatina mitiga la disfunción de la barrera endotelial in vitro e in vivo.
  • Explorar los mecanismos de acción de la simvastatina independientemente de la reducción de los lípidos.

Principales métodos:

  • La vena umbilical humana y las células endoteliales aórticas fueron tratadas con simvastatina.
  • La función de la barrera endotelial se evaluó midiendo la peroxidasa y el paso de LDL.
  • Los conejos hiperlipidémicos hereditarios de Watanabe fueron tratados con simvastatina, y se evaluó la fuga vascular utilizando la prueba de exclusión de colorante azul de Evans.

Principales resultados:

  • La simvastatina (5 micromol/L) redujo significativamente la disfunción de la barrera endotelial inducida por la trombina en in vitro en un 55%.
  • La simvastatina, dependiendo de la dosis y el tiempo, disminuyó la formación de fibra de estrés y la asociación de la membrana RhoA.
  • En conejos, el tratamiento con simvastatina redujo la fuga vascular aórtica sin alterar el tamaño de la lesión aterosclerótica.

Conclusiones:

  • La simvastatina mejora la función de la barrera endotelial in vitro e in vivo en altas concentraciones.
  • Estos hallazgos apoyan los efectos beneficiosos de la simvastatina en los eventos coronarios agudos a través de mecanismos no reductores de lípidos.
  • El impacto de la simvastatina en la integridad de la barrera endotelial ofrece una nueva perspectiva terapéutica.