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Increased proliferation of endothelial cells with overexpression of soluble TNF-alpha receptor I gene.
Sugano, Masahiro; Tsuchida, Keiko; Tomita, Hideharu; Makino, Naoki.
Affiliation
  • Sugano M; Department of Bioclimatology and Medicine, Medical Institute of Bioregulation Kyushu University, 4546 Tsurumihara, Beppu, Oita 874-0838, Japan. massy@tsurumi.beppu.kyushu-u.ac.jp
Atherosclerosis ; 162(1): 77-84, 2002 May.
Article in En | MEDLINE | ID: mdl-11947900
Vascular endothelial growth factor (VEGF) can overcome a potential anti-angiogenic effect of TNF-alpha by inhibiting endothelial apoptosis induced by this cytokine. Soluble TNF-alpha receptor I (sTNFRI) is an extracellular domain of TNFRI and antagonizes the activity of TNF-alpha. Here we report that sTNFRI is able to stimulate the growth of endothelial cells not by antagonizing TNF-alpha. Exogenously added recombinant human sTNFRI stimulated significantly more cell growth of human umbilical venous endothelial cells (HUVEC) with a low dose (50-200 pg/ml) compared with smooth muscle cells. In contrast, monoclonal antibody against TNF-alpha did not stimulate growth of human HUVEC. The sTNFRI expression plasmid (pcDNA3.1 plasmid) was introduced into the cell culture using OPTI-MEM, lipofectin and transferrin. Growth of HUVEC transfected with sTNFRI vector also increased significantly compared with those transfected with control vector. HUVEC transfected with sTNFRI vector increased the extracellular domain of TNFRI mRNA levels, but did not affect the intracellular domain of TNFRI mRNA levels. Accumulation of sTNFRI significantly increased in conditioned medium from HUVEC transfected with sTNFRI vector compared with those transfected with control vector. HUVEC transfected with sTNFRI vector not only increased sTNFRI but also prevented shedding of sTNFRI from TNFRI. The TNF-alpha -induced internucleosomic fragmentation was also significantly prevented in HUVEC transfected with sTNFRI vector compared with those transfected with control vector. These results suggest that instead of growth factors such as VEGF, local transfection of the sTNFRI gene may have potential therapeutic value in vascular diseases in which TNF-alpha is also usually highly expressed.
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Collection: 01-internacional Database: MEDLINE Main subject: Endothelium, Vascular / Antigens, CD / Tumor Necrosis Factor-alpha / Receptors, Tumor Necrosis Factor Type of study: Diagnostic_studies Limits: Humans Language: En Journal: Atherosclerosis Year: 2002 Document type: Article Affiliation country: Japan Country of publication: Ireland
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Collection: 01-internacional Database: MEDLINE Main subject: Endothelium, Vascular / Antigens, CD / Tumor Necrosis Factor-alpha / Receptors, Tumor Necrosis Factor Type of study: Diagnostic_studies Limits: Humans Language: En Journal: Atherosclerosis Year: 2002 Document type: Article Affiliation country: Japan Country of publication: Ireland