Short-term delivery of anti-PlGF antibody delays progression of atherosclerotic plaques to vulnerable lesions

Aims: placental growth factor (PlGF), a homologue of vascular endothelial growth factor, is a pleiotropic cytokine with a pro-inflammatory activity. Previous gene-inactivation studies revealed that the loss of PlGF delays atherosclerotic lesion development and inhibits macrophage infiltration, but t...

Descripción completa

Detalles Bibliográficos
Autores: Roncal Mancho, Carmen, Buysschaert, Ian, Gerdes, Norbert, Georgiadou, Maria, Ovchinnikova, Olga, Fischer, Christian, Stassen, Jean-Marie, Moons, Lieve, Collen, Désiré, De Bock, Katrien, Hansson, Göran K., Carmeliet, Peter
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2009
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/56169
Acceso en línea:https://hdl.handle.net/2454/56169
Access Level:acceso abierto
Palabra clave:PlGF
Atherosclerosis
Inflammation
PlGF neutralization
Descripción
Sumario:Aims: placental growth factor (PlGF), a homologue of vascular endothelial growth factor, is a pleiotropic cytokine with a pro-inflammatory activity. Previous gene-inactivation studies revealed that the loss of PlGF delays atherosclerotic lesion development and inhibits macrophage infiltration, but the activity of an anti-PlGF antibody (αPlGF mAb) has not been evaluated yet. Methods and results: we characterized the potential of short-term delivery of αPlGF mAb in inhibiting lesion development in ApoE-deficient mice (apoE−/−) and in CD4:TGFβRIIDN x apoE−/− mice, a more severe atherosclerosis model. Short-term treatment of αPlGF mAb reduces early atherosclerotic plaque size and inflammatory cell infiltration in the lesion. Conclusion: these pharmacological αPlGF mAb results confirm previous genetic evidence that inhibition of PlGF slows down early atherosclerotic lesion development. Furthermore, the phenocopy of genetic and pharmacological loss-of-function strategies underscores that αPlGF acts by selectively neutralizing PlGF.