Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis

Kazuhide Watanabe, Yasuhiro Hasegawa, Hiroshi Yamashita, Kazue Shimizu, Yuanying Ding, Mayumi Abe, Hideki Ohta, Keiichi Imagawa, Kanji Hojo, Hideo Maki, Hikaru Sonoda, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

248 Citations (Scopus)

Abstract

Negative feedback is a crucial physiological regulatory mechanism, but no such regulator of angiogenesis has been established. Here we report a novel angiogenesis inhibitor that is induced in endothelial cells (ECs) by angiogenic factors and inhibits angiogenesis in an autocrine manner. We have performed cDNA microarray analysis to survey VEGF-inducible genes in human ECs. We characterized one such gene, KIAA1036, whose function had been uncharacterized. The recombinant protein inhibited migration, proliferation, and network formation by ECs as well as angiogenesis in vivo. This inhibitory effect was selective to ECs, as the protein did not affect the migration of smooth muscle cells or fibroblasts. Specific elimination of the expression of KIAA1036 in ECs restored their responsiveness to a higher concentration of VEGF. The expression of KIAA1036 was selective to ECs, and hypoxia or TNF-α abrogated its inducible expression. As this molecule is preferentially expressed in ECs, we designated it "vasohibin." Transfection of Lewis lung carcinoma cells with the vasohibin gene did not affect the proliferation of cancer cells in vitro, but did inhibit tumor growth and tumor angiogenesis in vivo. We propose vasohibin to be an endothelium-derived negative feedback regulator of angiogenesis.

Original languageEnglish
Pages (from-to)898-907
Number of pages10
JournalJournal of Clinical Investigation
Volume114
Issue number7
DOIs
Publication statusPublished - 2004 Oct

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis'. Together they form a unique fingerprint.

Cite this