Short-term delivery of anti-PlGF antibody delays progression of atherosclerotic plaques to vulnerable lesions
C Roncal, I Buysschaert, N Gerdes… - Cardiovascular …, 2010 - academic.oup.com
C Roncal, I Buysschaert, N Gerdes, M Georgiadou, O Ovchinnikova, C Fischer, JM Stassen…
Cardiovascular research, 2010•academic.oup.comAbstract 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 …
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 …
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.
Oxford University Press