BROWSE

Related Researcher

Author

Suh, Pann-Ghill
BioSignal Network Lab (BSN)
Research Interests
  • Signal transduction, cancer, metabolism, phospholipase C

ITEM VIEW & DOWNLOAD

Endothelial Deletion of Phospholipase D2 Reduces Hypoxic Response and Pathological Angiogenesis

Cited 1 times inthomson ciCited 0 times inthomson ci
Title
Endothelial Deletion of Phospholipase D2 Reduces Hypoxic Response and Pathological Angiogenesis
Author
Ghim, JaewangMoon, Jin-SookLee, Chang SupLee, JunyeopSong, ParkyongLee, AreumJang, Jin-HyeokKim, DayeaYoon, Jong HyukKoh, Young JunChelakkot, ChaithanyaKang, Byung JunKim, Jung-MinKim, Kyung LockYang, Yong RyoulKim, YoungmiKim, Sun-HeeHwang, DaeheeSuh, Pann-GhillKoh, Gou YoungKong, Young-YunRyu, Sung Ho
Keywords
Angiogenesis; Endothelial cell; Hypoxia-inducible factor-1; Phospholipase D2
Issue Date
201408
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Citation
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, v.34, no.8, pp.1697 - 1703
Abstract
Objective - Aberrant regulation of the proliferation, survival, and migration of endothelial cells (ECs) is closely related to the abnormal angiogenesis that occurs in hypoxia-induced pathological situations, such as cancer and vascular retinopathy. Hypoxic conditions and the subsequent upregulation of hypoxia-inducible factor-1α and target genes are important for the angiogenic functions of ECs. Phospholipase D2 (PLD2) is a crucial signaling mediator that stimulates the production of the second messenger phosphatidic acid. PLD2 is involved in various cellular functions; however, its specific roles in ECs under hypoxia and in vivo angiogenesis remain unclear. In the present study, we investigated the potential roles of PLD2 in ECs under hypoxia and in hypoxia-induced pathological angiogenesis in vivo. Approach And Results - Pld2 knockout ECs exhibited decreased hypoxia-induced cellular responses in survival, migration, and thus vessel sprouting. Analysis of hypoxia-induced gene expression revealed that PLD2 deficiency disrupted the upregulation of hypoxia-inducible factor-1α target genes, including VEGF, PFKFB3, HMOX-1, and NTRK2. Consistent with this, PLD2 contributed to hypoxia-induced hypoxia-inducible factor-1α expression at the translational level. The roles of PLD2 in hypoxia-induced in vivo pathological angiogenesis were assessed using oxygen-induced retinopathy and tumor implantation models in endothelial-specific Pld2 knockout mice. Pld2 endothelial-specific knockout retinae showed decreased neovascular tuft formation, despite a larger avascular region. Tumor growth and tumor blood vessel formation were also reduced in Pld2 endothelial-specific knockout mice. Conclusions - Our findings demonstrate a novel role for endothelial PLD2 in the survival and migration of ECs under hypoxia via the expression of hypoxia-inducible factor-1α and in pathological retinal angiogenesis and tumor angiogenesis in vivo.
URI
Go to Link
DOI
http://dx.doi.org/10.1161/ATVBAHA.114.303416
ISSN
1079-5642
Appears in Collections:
SLS_Journal Papers

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qr_code

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU