Short-term delivery of anti-PlGF antibody delays progression of atherosclerotic plaques to vulnerable lesions.
OBJECTIVE
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 (alphaPlGF mAb) has not been evaluated yet.


RESULTS
We characterized the potential of short-term delivery of alphaPlGF mAb in inhibiting lesion development in ApoE-deficient mice (apoE(-/-)) and in CD4:TGFbetaRII(DN) x apoE(-/-) mice, a more severe atherosclerosis model. Short-term treatment of alphaPlGF mAb reduces early atherosclerotic plaque size and inflammatory cell infiltration in the lesion.


CONCLUSIONS
These pharmacological alphaPlGF 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 alphaPlGF acts by selectively neutralizing PlGF.
Roncal
Carmen
C
Vesalius Research Center, VIB, KULeuven, Campus Gasthuisberg, Herestraat 49, Box 912, 3000 Leuven, Belgium.
Buysschaert
Ian
I
Gerdes
Norbert
N
Georgiadou
Maria
M
Ovchinnikova
Olga
O
Fischer
Christian
C
Stassen
Jean-Marie
JM
Moons
Lieve
L
Collen
Désiré
D
De Bock
Katrien
K
Hansson
Göran K
GK
Carmeliet
Peter
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000276:immunology* / Q000378:metabolism*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D019010:Vascular Cell Adhesion Molecule-1; D000072483:Placenta Growth Factor