VEGF-enhanced proliferation under hypoxia an autocrine mechanism in human vascular smooth muscle cells

• Osada-Oka Mayuko

  Department of Pathological Biochemistry, Kyoto Pharmaceutical University.

• Ikeda Takako

  Department of Pathological Biochemistry, Kyoto Pharmaceutical University.

• Imaoka Susumu

  Nanobiotechnology Research Center and Department of Bioscience, School of Science and Technology, Kwansei Gakuin University.

• Akiba Satoshi

  Department of Pathological Biochemistry, Kyoto Pharmaceutical University.

• Sato Takashi

  Department of Pathological Biochemistry, Kyoto Pharmaceutical University.

書誌事項

タイトル別名

• VEGF-Enhanced Proliferation under Hypoxia by an Autocrine Mechanism in Human Vascular Smooth Muscle Cells

抄録

Aim: Atherosclerotic lesions are reported to be hypoxic. Since hypoxia is known to induce the production of growth factors, such as vascular endothelial growth factor (VEGF), we examined the implication of hypoxia-induced VEGF in the proliferation of human coronary artery smooth muscle cells (CASMCs).<BR>Methods: Cells were cultured under hypoxic conditions (1% O₂, 5% CO₂) and several responses were measured.<BR>Results: Under hypoxic conditions, the mRNA and protein levels of VEGF, and the mRNA level of VEGF receptor-1 (VEGFR-1) increased with an increase in hypoxia-inducible factor-1α (HIF-1α) protein, and considerable amounts of VEGF were secreted. Hypoxia enhanced the incorporation of [³H]-thymidine by CASMCs, which was completely inhibited by a neutralizing antibody against VEGF. A neutralizing antibody against NADPH-cytochrome P-450 reductase (NPR), which contributes to the stabilization of HIF-1α, also attenuated hypoxia-stimulated proliferation. In NPR-knockdown cells, the expression of VEGF, proliferation, and transcriptional activity were attenuated, whereas in NPR-overexpressing cells, they were enhanced.<BR>Conclusion: Hypoxia-induced proliferation of CASMCs is mediated through the expressions of VEGF and VEGFR-1 in an autocrine mechanism. Their expressions are dependent on the stabilization of HIF-1α, which is regulated by NPR. We suggest that hypoxia and hypoxia-induced VEGF expression are involved in the pathogenesis of progressive atherosclerosis.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ

  Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ 15 (1), 26-33, 2008

  一般社団法人 日本動脈硬化学会

キーワード

• Hypoxia
• Proliferation
• VEGF
• Vascular smooth muscle cells

詳細情報

• CRID: 1390282679407940992
• NII論文ID: 10022607720
• NII書誌ID: AA11018976
• DOI: 10.5551/jat.e533
• ISSN: 18803873
• ISSN: 13403478
• Web Site: https://search.jamas.or.jp/link/ui/2008187964
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可