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Inducción específica por región y tipo de las metaloproteinasas de matriz en la remodelación posterior al infarto de
Eric M Wilson1, Sina L Moainie, Julia M Baskin
1Medical University of South Carolina, Charleston, SC 29425, USA.
Circulation
|May 29, 2003
Resumen
Las metaloproteinasas matriciales (MMP) muestran cambios específicos de la región después del infarto de miocardio (IM), que afectan a la remodelación cardíaca. Dirigirse a estos MMP y sus inhibidores (TIMPs) puede ofrecer nuevas estrategias terapéuticas para la recuperación posterior al infarto de miocardio.
Área de la Ciencia:
- Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular
- La bioquímica es la bioquímica.
- Fisiopatología Fisiopatología.
Sus antecedentes:
- Las metaloproteinasas matriciales (MMP) están implicadas en la remodelación cardíaca adversa después del infarto de miocardio (IM).
- Anteriormente no se había caracterizado la distribución espacial y específica del tipo de MMP dentro del miocardio post-MI.
Objetivo del estudio:
- Investigar los cambios específicos de región y tipo en los MMP y sus inhibidores (TIMPs) dentro del miocardio después del infarto de miocardio.
- Para correlacionar estos cambios moleculares con alteraciones en la geometría cardíaca regional.
Principales métodos:
- Se utilizó la sonomicrometría para medir los cambios regionales en la longitud del segmento en 7 regiones miocárdicas distintas en ovejas después del IM.
- Inmunoblotting cuantificó la abundancia relativa de varios MMPs y TIMPs en regiones remotas, de transición y MI.
Principales resultados:
- Se observaron aumentos significativos en la longitud del segmento en todas las regiones, más pronunciados en la zona de MI.
- Se encontraron patrones distintos de expresión de MMP: MMP-1 y MMP-9 disminuyeron en las zonas de transición e IM, mientras que MMP-13, MMP-8 y MT1-MMP aumentaron significativamente en las zonas de transición e IM.
- La abundancia de TIMP disminuyó en la zona de transición y se volvió indetectable en la zona de IM, lo que indica una pérdida de inhibición de MMP.
Conclusiones:
- Los cambios en la geometría cardíaca después del infarto de miocardio están asociados con alteraciones específicas en los niveles de MMP.
- Una inducción específica de la región de MMPs, junto con una disminución de TIMPs, sugiere una pérdida de control inhibitorio en el miocardio post-MI.
- Dirigirse al desequilibrio regional de MMPs y TIMPs presenta una vía terapéutica potencial para manejar la remodelación adversa después del MI.
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