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Proproteína sérica convertasa subtilisina/kexina tipo 9 y receptor de lipoproteína de baja densidad de la superficie

Hagai Tavori¹, Daping Fan, John L Blakemore

¹Vanderbilt University, Cardiovascular Medicine, Nashville, TN 37232-6300, USA.

|May 22, 2013

Resumen

El receptor de lipoproteínas de baja densidad (LDL) (LDLR) es la vía principal para la eliminación de la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9). Esta regulación recíproca entre LDLR y PCSK9 controla los niveles de colesterol.

Área de la Ciencia:

La bioquímica es la bioquímica.
Biología Molecular Biología Molecular
Ciencias Cardiovasculares Ciencias Cardiovasculares

Sus antecedentes:

La proproteína convertasa subtilisina/kexina tipo 9 (PCSK9) regula la degradación del receptor de lipoproteínas de baja densidad (LDLR), que tiene un impacto en el colesterol sérico.
La LDLR defectuosa conduce a la hipercolesterolemia, pero no afecta el aclaramiento de PCSK9.

Objetivo del estudio:

Investigar las interacciones recíprocas entre PCSK9 y LDLR.
Para determinar sus efectos combinados sobre los niveles de colesterol sérico.

Principales métodos:

Generación de ratones transgénicos que expresan PCSK9 humano.
Análisis de la degradación de LDLR en varios tejidos (hígado, riñón, suprarrenal).
Medición de los niveles séricos de PCSK9 y colesterol en ratones de tipo salvaje, LDLR(-/-), y LDLR(+/-).

Principales resultados:

PCSK9 humano causó principalmente la degradación de LDLR en el hígado, a pesar de la expresión renal.
PCSK9 aumentó la secreción hepática de lipoproteínas independientemente de la LDLR.
La expresión de PCSK9 elevaba los niveles séricos de PCSK9, mientras que la expresión de LDLR los disminuía.
El aclaramiento de PCSK9 fue significativamente más rápido en presencia de LDLR funcional.

Conclusiones:

La LDLR es la principal vía para la eliminación de PCSK9.
Existe una relación reguladora recíproca entre LDLR y PCSK9.
Esta interacción rige el PCSK9 sérico, la expresión hepática de LDLR y, en última instancia, los niveles séricos de LDL.

Palabras clave:

Los receptores de LDL también son receptores de LDL.La proteína Pcsk9 es una proteína El colesterol colesterol colesterol es el colesterol.Las lipoproteínas son lipoproteínas.modelo de ratón modelo de ratón modelo de ratón

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