Inflammatory cells and chemokines sustain FGF2-induced angiogenesis.
Angiogenesis and inflammation are closely integrated processes in a number of physiological and pathological conditions, including wound healing, psoriasis, diabetic retinopathy, rheumatoid arthritis, arteriosclerosis, and cancer. Fibroblast growth factor-2 (FGF2) belongs to the family of the heparin-binding FGF growth factors. FGF2 exerts its pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. Elevated levels of FGF2 have been implicated in the pathogenesis of several diseases characterized by a deregulated angiogenic/inflammatory response. FGF2 induces the expression of a wide repertoire of inflammation-related genes in endothelial cells, including pro-inflammatory cytokines/chemokines and their receptors, endothelial cell adhesion molecules, and components of the prostaglandin pathway. Consistent with this pro-inflammatory signature, in vivo evidence points to a non-redundant role for chemokines and infiltrating monocytes/macrophages in FGF2-driven neovascularization. This review will focus on the cross-talk between FGF2 and the inflammatory response in the modulation of blood vessel growth.
Presta
Marco
M
Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Italy. presta@med.unibs.it
Andrés
Germán
G
Leali
Daria
D
Dell'Era
Patrizia
P
Ronca
Roberto
R
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018925:Chemokines / Q000502:physiology*; D002633:Chemotaxis; D002642:Chick Embryo; D042783:Endothelial Cells / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D020286:Pericytes / Q000502:physiology; D011453:Prostaglandins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D015815:Cell Adhesion Molecules; D018925:Chemokines; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D011453:Prostaglandins; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2