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Inhibition of Fibroblast-Induced Angiogenic Phenotype of Cultured Endothelial Cells by the Overexpression of Tissue Inhibitor of Metalloproteinase (TIMP)-3

Ma D.H.-K.a,c · Chen J.-I.b · Zhang F.c · Hwang D.G.c · Chen J.-K.b
aDepartment of Ophthalmology, Chang-Gung Memorial Hospital, bDepartment of Physiology, College of Medicine, Chang-Gung University, Kweishan, Taoyuan, Taiwan; cOcular Cell and Gene Therapy Laboratory, Department of Ophthalmology, University of California, San Francisco, Calif., USA J Biomed Sci 2003;10:526–534 (DOI:10.1159/000072380)


In this study, we examined the effect of overexpression of tissue inhibitor of metalloproteinase (TIMP)-3 on the angiogenic phenotype expressed by vascular endothelial cells (ECs). ECs were infected with a recombinant adenovirus carrying the TIMP-3 gene at various multiplicities of infection, and TIMP-3 expression by transfected cells was confirmed by Western blotting and reverse zymography. At transfection doses of 6.25, 12.5, 25, 50 and 100 multiplicity of infection, EC migration was reduced to 66, 45, 25, 17 and 5%, respectively, of that of the control. At the multiplicity of infection of 20, capillary tube length was reduced by 80% compared to that of the control. Thus, expression of TIMP-3 by ECs effectively inhibited EC migration and tube formation. Overexpression of TIMP-3 by ECs may be considered a gene therapy strategy for the treatment of pathological angiogenesis such as cancer and diabetic retinopathy.


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