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Impacto de la eliminación plasmática oxidada de lipoproteínas de baja densidad en la aterosclerosis
Yasushi Ishigaki1, Hideki Katagiri, Junhong Gao
1Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan.
Circulation
|June 19, 2008
Resumen
Dirigirse a la eliminación de LDL oxidado (oxLDL), no solo al colesterol LDL total, inhibe significativamente la progresión de la aterosclerosis. Este estudio muestra que la mejora del receptor de oxLDL LOX-1 en el hígado previene la enfermedad arterial en ratones.
Área de la Ciencia:
- Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular
- La aterosclerosis es la aterosclerosis.
- El metabolismo de los lípidos.
Sus antecedentes:
- La terapia con estatinas reduce el colesterol LDL, reduciendo la mortalidad cardiovascular.
- La LDL oxidada (oxLDL) está implicada en el desarrollo de la aterosclerosis.
- El impacto específico de la reducción de oxLDL solo en la atherogénesis no se entiende completamente.
Objetivo del estudio:
- Para investigar el papel aterogénico de oxLDL.DL.
- Para determinar si la orientación oxLDL tiene un impacto directo en la aterosclerosis.
- Explorar la eficacia de la expresión hepática del receptor oxLDL 1 (LOX-1) similar a la lectina en la prevención de la aterosclerosis.
Principales métodos:
- La expresión hepática mediada por adenovirus de LOX-1 en ratones con deficiencia de apolipoproteína E.
- Evaluación de la progresión de la lesión aterosclerótica a través de la tinción Oil Red O.
- Medición de los niveles plasmáticos de oxLDL, proteína quimiotáctica monocítica-1, peróxido lipídico y adiponectina.
Principales resultados:
- La expresión hepática de LOX-1 aumentó con éxito la absorción de oxLDL en el hígado.
- Los niveles plasmáticos de oxLDL se redujeron significativamente transitoriamente en ratones que expresaban LOX-1.
- La progresión de la lesión aterosclerótica fue casi completamente inhibida en ratones LOX-1 en comparación con los controles.
- Los marcadores sistémicos de estrés oxidativo disminuyeron, lo que se indica por la reducción de la proteína quimiotáctica monocítica-1 y el peróxido lipídico, y el aumento de la adiponectina.
Conclusiones:
- La LDL oxidada juega un papel importante en la conducción de la aterosclerosis.
- Dirigirse a la eliminación de oxLDL, particularmente a través de la LOX-1 hepática, es una estrategia terapéutica prometedora.
- La reducción de oxLDL puede prevenir la progresión de la aterosclerosis incluso con el colesterol LDL persistentemente alto.
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