Neovascularization: General remarks

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Neovascularization in adults is thought to be a mixed phenomenon of angiogenesis and vasculogenesis. Angiogenesis is the formation of neo-vessels from pre-existing vessels by sprouting and/or intussusception. Vasculogenesis is the differentiation of endothelial progenitor cells to endothelial cells (ECs) and subsequent formation of primary vascular plexus. Neo-vessels can be maintained, but sometimes regress spontaneously. Neovascularization occurs in a wide range of pathophysiological states, including cancer. Neovascularization in cancer correlates with cancer growth and its distant metastasis. Therefore, the effective inhibition of neovascularization is thought to be one of the promising strategies for cancer therapy. In contrast, neovascularization (vascular regeneration) is anticipated for the treatment of ischemic diseases including arteriosclerotic occlusion of the lower limbs or angina pectoris/myocardial infarction in order to rescue the ischemic tissue by developing collateral circulation. Neovascularization and vascular regression are thought to be regulated by the balance of stimulators and inhibitors. Numerous molecules have been reported to be involved in the regulation of neovascularization. Among them, endothelium-specific factors and their signal transducing receptors play principal roles. They include vascular endothelial growth factor (VEGF), Flt-1 (VEGF receptor-1), KDR/Flk-1 (VEGF receptor-2), angiopoietin-1, angiopoietin-2, and TIE-2 receptor. Among them, the enhanced expression of VEGF and angiopoietin-2 are common features in cancer. Flt-4 (VEGF receptor-3) is preferentially expressed in lymphatic ECs, and their ligands, VEGF-C and VEGF-D, are involved in lymphangiogenesis. Recent observations suggest that the enhanced expression of VEGF-C and/or VEGF-D in cancer correlates with lymph node metastasis. Therefore, the regulation of this system appears promising for the regulation of lymph node metastasis.

Original languageEnglish
Pages (from-to)631-636
Number of pages6
Issue number6
Publication statusPublished - 2001


  • Lymphangiogenesis
  • Neovascularization
  • Vascular regeneration
  • Vascular regression


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