Effect of antibody-mediated connective tissue growth factor neutralization on lung edema in ventilator-induced lung injury in rats.
Mol Med
; 30(1): 68, 2024 May 22.
Article
en En
| MEDLINE
| ID: mdl-38778274
ABSTRACT
BACKGROUND:
Acute respiratory distress syndrome (ARDS) is characterized by alveolar edema that can progress to septal fibrosis. Mechanical ventilation can augment lung injury, termed ventilator-induced lung injury (VILI). Connective tissue growth factor (CTGF), a mediator of fibrosis, is increased in ARDS patients. Blocking CTGF inhibits fibrosis and possibly vascular leakage. This study investigated whether neutralizing CTGF reduces pulmonary edema in VILI.METHODS:
Following LPS administration, rats were mechanically ventilated for 6 h with low (6 mL/kg; low VT) or moderate (10 mL/kg; mod VT) tidal volume and treated with a neutralizing CTGF antibody (FG-3154) or placebo lgG (vehicle). Control rats without LPS were ventilated for 6 h with low VT. Lung wet-to-dry weight ratio, FITC-labeled dextran permeability, histopathology, and soluble RAGE were determined.RESULTS:
VILI was characterized by reduced PaO2/FiO2 ratio (low VT 540 [381-661] vs. control 693 [620-754], p < 0.05), increased wet-to-dry weight ratio (low VT 4.8 [4.6-4.9] vs. control 4.5 [4.4-4.6], p < 0.05), pneumonia (low VT 30 [0-58] vs. control 0 [0-0]%, p < 0.05) and interstitial inflammation (low VT 2 [1-3] vs. control 1 [0-1], p < 0.05). FG-3154 did not affect wet-to-dry weight ratio (mod VT + FG-3154 4.8 [4.7-5.0] vs. mod VT + vehicle 4.8 [4.8-5.0], p > 0.99), extravasated dextrans (mod VT + FG-3154 0.06 [0.04-0.09] vs. mod VT + vehicle 0.04 [0.03-0.09] µg/mg tissue, p > 0.99), sRAGE (mod VT + FG-3154 1865 [1628-2252] vs. mod VT + vehicle 1885 [1695-2159] pg/mL, p > 0.99) or histopathology.CONCLUSIONS:
'Double hit' VILI was characterized by inflammation, impaired oxygenation, pulmonary edema and histopathological lung injury. Blocking CTGF does not improve oxygenation nor reduce pulmonary edema in rats with VILI.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Edema Pulmonar
/
Lesión Pulmonar Inducida por Ventilación Mecánica
/
Factor de Crecimiento del Tejido Conjuntivo
Límite:
Animals
Idioma:
En
Revista:
Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Reino Unido