Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan.
The NG2 proteoglycan is expressed by nascent pericytes during the early stages of angiogenesis. To investigate the functional role of NG2 in neovascularization, we have compared pathological retinal and corneal angiogenesis in wild type and NG2 null mice. During ischemic retinal neovascularization, ectopic vessels protruding into the vitreous occur twice as frequently in wild type retinas as in NG2 null retinas. In the NG2 knock-out retina, proliferation of both pericytes and endothelial cells is significantly reduced, and the pericyte:endothelial cell ratio falls to 0.24 from the wild type value of 0.86. Similarly, bFGF-induced angiogenesis is reduced more than four-fold in the NG2 null cornea compared to that seen in the wild type retina. Significantly, NG2 antibody is effective in reducing angiogenesis in the wild type cornea, suggesting that the proteoglycan can be an effective target for anti-angiogenic therapy. These experiments therefore demonstrate both the functional importance of NG2 in pericyte development and the feasibility of using pericytes as anti-angiogenic targets.
Ozerdem
Ugur
U
La Jolla Institute for Molecular Medicine, Vascular Biology Division, La Jolla, California, USA. ozerdem@ljimm.org
Stallcup
William B
WB
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000941:Antigens / Q000235:genetics / Q000502:physiology*; D003315:Cornea / Q000098:blood supply / Q000473:pathology; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007511:Ischemia / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D020286:Pericytes / Q000187:drug effects* / Q000502:physiology; D011509:Proteoglycans / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000473:pathology; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000906:Antibodies; D000941:Antigens; D016222:Fibroblast Growth Factor 2; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4