Increased expression of syndecan-1 protects against cardiac dilatation and dysfunction after myocardial infarction.
Circulation
; 115(4): 475-82, 2007 Jan 30.
Article
en En
| MEDLINE
| ID: mdl-17242279
ABSTRACT
BACKGROUND:
The cell-associated proteoglycan syndecan-1 (Synd1) closely regulates inflammation and cell-matrix interactions during wound healing and tumorigenesis. The present study investigated whether Synd1 may also regulate cardiac inflammation, matrix remodeling, and function after myocardial infarction (MI). METHODS ANDRESULTS:
First, we showed increased protein and mRNA expression of Synd1 from 24 hours on, reaching its maximum at 7 days after MI and declining thereafter. Targeted deletion of Synd1 resulted in increased inflammation and accelerated, yet functionally adverse, infarct healing after MI. In concordance, adenoviral gene expression of Synd1 protected against exaggerated inflammation after MI, mainly by reducing transendothelial adhesion and migration of leukocytes, as shown in vitro. Increased inflammation in the absence of Synd1 resulted in increased monocyte chemoattractant protein-1 expression, increased activity of matrix metalloproteinase-2 and -9, and decreased activity of tissue transglutaminase, associated with increased collagen fragmentation and disorganization. Exaggerated inflammation and adverse matrix remodeling in the absence of Synd1 increased cardiac dilatation and impaired systolic function, whereas gene overexpression of Synd1 reduced inflammation and protected against cardiac dilatation and failure.CONCLUSIONS:
Increased expression of Synd1 in the infarct protects against exaggerated inflammation and adverse infarct healing, thereby reducing cardiac dilatation and dysfunction after MI in mice.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cardiomiopatía Dilatada
/
Remodelación Ventricular
/
Sindecano-1
/
Infarto del Miocardio
Límite:
Animals
Idioma:
En
Revista:
Circulation
Año:
2007
Tipo del documento:
Article
País de afiliación:
Países Bajos