Blockage of the formation of new blood vessels by recombinant human endostatin contributes to the regression of rat adjuvant arthritis.
The formation of new blood vessels permits a supply of nutrients and oxygen to the proliferating synovial cells and augmented inflammatory cell mass in rheumatoid arthritis (RA). Angiogenesis inhibition is not dependent on a down-regulated immune system. Therefore, angiogenesis is an attractive target in treating rheumatoid arthritis. To confirm the effect of recombinant human endostatin, an angiogenesis inhibitor, on inflammatory angiogenesis and to elucidate the related mechanisms, rat adjuvant arthritis model induced by Freund's complete adjuvant was used. The secondary arthritis was evaluated by using clinical scores and determining the volume of hind paw swelling. The number of new blood vessels was counted under microscope based on HE (hematoxylin and eosin) staining and positive immunoreactivity of factor VIII related antigen. factor VIII related antigen and vascular endothelial growth factor (VEGF) expressions in synovial tissue were determined by using immunohistochemistry. It was found that endostatin attenuated rat secondary paw swelling induced by Freund's complete adjuvant in a dose-dependent manner. Meanwhile, the number of new blood vessels in synovial tissue stained with HE was reduced after treatment with endostatin, which was proved by the positive immunostaining of factor VIII related antigen. Further, endostatin decreased the expression of VEGF in both cartilage and synovial tissue. These suggest that endostatin inhibiting VEGF expression contributes to the regression of rat adjuvant arthritis.
Yue
Li
L
Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, PR China.
Shen
Yu-Xian
YX
Feng
Li-Jie
LJ
Chen
Fei-Hu
FH
Yao
Hong-Wei
HW
Liu
Li-Hua
LH
Wu
Qiang
Q
Wang
Hua
H
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D043169:Endostatins / Q000494:pharmacology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A