Role of the low-affinity leukotriene B 4 receptor BLT2 in VEGF-induced angiogenesis

Geun Young Kim, Jin Wook Lee, Sung Hoon Cho, Ji Min Seo, Jae Hong Kim

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

OBJECTIVE-: The leukotriene B4 (LTB4) receptor BLT2 is expressed in endothelium, but no clear physiological function for it has yet been identified, especially in vascular angiogenesis. The purpose of this study is to characterize the potential function of BLT2 in vascular endothelial growth factor (VEGF)-induced angiogenesis. METHODS AND RESULTS-: VEGF significantly upregulates BLT2 expression in human umbilical vein endothelial cells (HUVECs), and BLT2 knockdown by siRNA or inhibition of BLT2 by a specific BLT2 antagonist LY255283 attenuates VEGF-induced angiogenesis, which was determined by its effect on the formation of tube-like structures and on transmigration. The role of BLT2 in VEGF-induced angiogenesis was more evident in vivo, where BLT2 inhibition by LY255283 almost completely blocked VEGF-induced vessel formation in Matrigel-plug assays. In addition, we found that VEGF upregulates synthesis of the BLT2 ligand, 12(S)-hydroxyeicosatetraenoic acid (HETE). siRNA knockdown of 12-lipoxygenase (12-LO) expression attenuates VEGF-induced angiogenesis in HUVECs, and the addition of 12(S)-HETE to the 12-LO knockdown-HUVECs restores VEGF-induced angiogenesis. The activation of BLT2 itself by either 12(S)-HETE or LTB4 evoked significant angiogenic phenotypes, both in vitro and in vivo. CONCLUSION-: Our findings indicate that BLT2 plays an essential role in mediating VEGF-induced angiogenesis.

Original languageEnglish
Pages (from-to)915-920
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number6
DOIs
Publication statusPublished - 2009 Jun

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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