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 (alphaPlGF mAb) has not been evaluated yet. METHODS AND 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. CONCLUSION: 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.
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 PlGFdelays atherosclerotic lesion development and inhibits macrophage infiltration, but the activity of an anti-PlGF antibody (alphaPlGF mAb) has not been evaluated yet. METHODS AND 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. CONCLUSION: 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.
Authors: Mehdi Rambod; Gunnar H Heine; Sarah Seiler; Elizabeth A Dominic; Kyrill S Rogacev; Rama Dwivedi; Ali Ramezani; Maria R Wing; Richard L Amdur; Danilo Fliser; Dominic S Raj Journal: Atherosclerosis Date: 2014-08-12 Impact factor: 5.162
Authors: Jacqueline G Parchem; Keizo Kanasaki; Megumi Kanasaki; Hikaru Sugimoto; Liang Xie; Yuki Hamano; Soo Bong Lee; Vincent H Gattone; Samuel Parry; Jerome F Strauss; Vesna D Garovic; Thomas F McElrath; Karen H Lu; Baha M Sibai; Valerie S LeBleu; Peter Carmeliet; Raghu Kalluri Journal: J Clin Invest Date: 2018-10-08 Impact factor: 14.808
Authors: Ming Wu; Peter Pokreisz; Melissa Swinnen; Ellen Caluwe; Hilde Gillijns; Nina Vanden Driessche; Andrea Casazza; Erik Verbeken; Desire Collen; Stefan Janssens Journal: J Cardiovasc Transl Res Date: 2017-04-10 Impact factor: 4.132
Authors: Adam P McGraw; Jessamyn Bagley; Wei-Sheng Chen; Carol Galayda; Heather Nickerson; Andrea Armani; Massimiliano Caprio; Peter Carmeliet; Iris Z Jaffe Journal: J Am Heart Assoc Date: 2013-02-22 Impact factor: 5.501