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Cardiovascular Research

Publication date: 2010-04
Volume: 86 Pages: 29 - 36
ISSN: 0008-6363, 1755-3245 PMID: 19952000
DOI: 10.1093/cvr/cvp380
Publisher: British Medical Association

Author:

Roncal, Carmen
Buysschaert, Ian ; Gerdes, Norbert ; Georgiadou, Maria ; Ovchinnikova, Olga ; Fischer, Christian ; Stassen, Jean-Marie ; Moons, Lieve ; Collen, Desire ; De Bock, Katrien ; Hansson, Göran ; Carmeliet, Peter

Keywords:

PlGF, atherosclerosis, inflammation, PlGF neutralization, Science & Technology, Life Sciences & Biomedicine, Cardiac & Cardiovascular Systems, Cardiovascular System & Cardiology, Atherosclerosis, Inflammation, PLACENTAL GROWTH-FACTOR, SMOOTH-MUSCLE-CELLS, MACROPHAGE ACCUMULATION, ADHESION MOLECULE-1, FACTOR EXPRESSION, IMMUNE-RESPONSE, GENE-EXPRESSION, DENDRITIC CELLS, DEFICIENT MICE, T-CELLS, Animals, Antibodies, Monoclonal, Aorta, Aortic Diseases, Apolipoproteins E, Disease Models, Animal, Disease Progression, Female, Macrophages, Mice, Mice, Mutant Strains, Muscle, Smooth, Vascular, Placenta Growth Factor, Pregnancy Proteins, Tunica Intima, Vascular Cell Adhesion Molecule-1, 1102 Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology

Abstract:

Aims: The vascular endothelial growth factor homologue placental growth factor (PlGF) is a pleiotropic cytokine, with a pro-inflammatory activity. Previous gene-inactivation studies revealed that loss of PlGF delays atherosclerotic lesion development and inhibits macrophage infiltration, but the activity of an anti-PlGF antibody (aPlGF mAb) has not been evaluated yet. Methods and Results: We characterized the potential of short-term delivery of aPlGF mAb in inhibiting lesion development in ApoE-deficient mice (apoE-/-) and in CD4:TGFßRIIDN x apoE-/- mice, a more severe atherosclerosis model. Short-term treatment of aPlGF mAb reduces early atherosclerotic plaque size and inflammatory cell infiltration in the lesion. Conclusions: These pharmacological aPlGF 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 aPlGF acts by selectively neutralizing PlGF.