PMID- 24497508
OWN - NLM
STAT- MEDLINE
DCOM- 20140415
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 111
IP  - 7
DP  - 2014 Feb 18
TI  - Transcriptional activation of hypoxia-inducible factor-1 (HIF-1) in myeloid cells 
      promotes angiogenesis through VEGF and S100A8.
PG  - 2698-703
LID - 10.1073/pnas.1320243111 [doi]
AB  - Emerging evidence indicates that myeloid cells are essential for promoting new 
      blood vessel formation by secreting various angiogenic factors. Given that 
      hypoxia-inducible factor (HIF) is a critical regulator for angiogenesis, we 
      questioned whether HIF in myeloid cells also plays a role in promoting 
      angiogenesis. To address this question, we generated a unique strain of 
      myeloid-specific knockout mice targeting HIF pathways using human S100A8 as a 
      myeloid-specific promoter. We observed that mutant mice where HIF-1 is 
      transcriptionally activated in myeloid cells (by deletion of the von 
      Hippel-Lindau gene) resulted in erythema, enhanced neovascularization in matrigel 
      plugs, and increased production of vascular endothelial growth factor (VEGF) in 
      the bone marrow, all of which were completely abrogated by either genetic or 
      pharmacological inactivation of HIF-1. We further found that monocytes were the 
      major effector producing VEGF and S100A8 proteins driving neovascularization in 
      matrigel. Moreover, by using a mouse model of hindlimb ischemia we observed 
      significantly improved blood flow in mice intramuscularly injected with 
      HIF-1-activated monocytes. This study therefore demonstrates that HIF-1 
      activation in myeloid cells promotes angiogenesis through VEGF and S100A8 and 
      that this may become an attractive therapeutic strategy to treat diseases with 
      vascular defects.
FAU - Ahn, G-One
AU  - Ahn GO
AD  - Division of Integrative Biosciences and Biotechnology, Pohang University of 
      Science and Technology, Pohang, Gyeongbuk 790-784, Korea.
FAU - Seita, Jun
AU  - Seita J
FAU - Hong, Beom-Ju
AU  - Hong BJ
FAU - Kim, Young-Eun
AU  - Kim YE
FAU - Bok, Seoyeon
AU  - Bok S
FAU - Lee, Chan-Ju
AU  - Lee CJ
FAU - Kim, Kwang Soon
AU  - Kim KS
FAU - Lee, Jerry C
AU  - Lee JC
FAU - Leeper, Nicholas J
AU  - Leeper NJ
FAU - Cooke, John P
AU  - Cooke JP
FAU - Kim, Hak Jae
AU  - Kim HJ
FAU - Kim, Il Han
AU  - Kim IH
FAU - Weissman, Irving L
AU  - Weissman IL
FAU - Brown, J Martin
AU  - Brown JM
LA  - eng
GR  - R01 CA149318/CA/NCI NIH HHS/United States
GR  - U01 HL099995/HL/NHLBI NIH HHS/United States
GR  - U01 HL099999/HL/NHLBI NIH HHS/United States
GR  - CA149318/CA/NCI NIH HHS/United States
GR  - U01HL099999/HL/NHLBI NIH HHS/United States
GR  - R01 CA086065/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140204
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Calgranulin A)
RN  - 0 (DNA Primers)
RN  - 0 (Drug Combinations)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Laminin)
RN  - 0 (Proteoglycans)
RN  - 0 (S100a8 protein, mouse)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 119978-18-6 (matrigel)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Blotting, Western
MH  - Calgranulin A/*metabolism
MH  - Collagen
MH  - Crosses, Genetic
MH  - DNA Primers/genetics
MH  - Drug Combinations
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Hindlimb/blood supply
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Ischemia/physiopathology
MH  - Laminin
MH  - Mice
MH  - Mice, Transgenic
MH  - Myeloid Cells/*metabolism
MH  - Neovascularization, Physiologic/*physiology
MH  - Polymerase Chain Reaction
MH  - Proteoglycans
MH  - Transcriptional Activation/genetics/*physiology
MH  - Vascular Endothelial Growth Factor A/*metabolism
PMC - PMC3932909
COIS- The authors declare no conflict of interest.
EDAT- 2014/02/06 06:00
MHDA- 2014/04/16 06:00
PMCR- 2014/08/18
CRDT- 2014/02/06 06:00
PHST- 2014/02/06 06:00 [entrez]
PHST- 2014/02/06 06:00 [pubmed]
PHST- 2014/04/16 06:00 [medline]
PHST- 2014/08/18 00:00 [pmc-release]
AID - 1320243111 [pii]
AID - 201320243 [pii]
AID - 10.1073/pnas.1320243111 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2698-703. doi: 
      10.1073/pnas.1320243111. Epub 2014 Feb 4.