- Paper Report
- Open Access
Modulation of angiogenesis by VEGF and placental growth factor
- Ewa Paleolog1
© Biomed Central Ltd 2002
- Received: 8 July 2002
- Published: 11 July 2002
Formation of new blood vessels ('angiogenesis') is central to the development of rheumatoid arthritis (RA), to supply nutrients and oxygen to the synovium. An understanding of angiogenesis is thus useful for the development of vascular targeted therapies for treatment of RA. This study assessed the role of placental growth factor (PlGF) and its receptor Flt1, which also binds the angiogenic factor VEGF (vascular endothelial growth factor).
PlGF and VEGF stimulated growth of new vessels in a mouse model of ischemic myocardial revascularisation. Human PlGF also significantly increased formation of collateral branches, following femoral artery ligation. Adenoviral transfer of PlGF into the skin of mouse ears caused formation of mature vessels, unlike VEGF, which leads to oedema and growth of unstable vascular structures. Anti-Flt-1 antibody inhibited vascularisation and growth of human tumours in nude mice, and reduced the size and growth of plaques in atherosclerosis-susceptible apolipoprotein-E-deficient mice. However, anti-Flt-1 failed to affect angiogenesis in the plaque and in the adventitia. More likely, in this model, anti-Flt-1 reduced inflammation by decreasing macrophage infiltration. Finally, anti-Flt-1 reduced the incidence of joint disease and development of clinical symptoms in the mouse collagen-induced arthritis model. Synovial infiltration by inflammatory cells and angiogenesis were reduced by anti-Flt-1.
Mouse models of angiogenesis (Matrigel and corneal micropocket assays), atherosclerosis (ApoE -/-) and collagen-induced arthritis . Transplantation of bone marrow, transduced with a green fluorescent protein-expressing vector. Adenoviral gene transfer of PlGF. Mouse models of myocardial and limb ischemia.
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