PMID- 19834107
OWN - NLM
STAT- MEDLINE
DCOM- 20100114
LR  - 20161125
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 30
IP  - 1
DP  - 2010 Jan
TI  - Adenosine modulates HIF-1alpha, VEGF, IL-8, and foam cell formation in a human 
      model of hypoxic foam cells.
PG  - 90-7
LID - 10.1161/ATVBAHA.109.194902 [doi]
AB  - OBJECTIVE: Foam cell (FC) formation by oxidized low-density lipoprotein (oxLDL) 
      accumulation in macrophages is crucial for development of atherosclerosis. 
      Hypoxia has been demonstrated in atherosclerosis and hypoxia-inducible factor-1 
      (HIF-1) has been shown to promote intraplaque angiogenesis and FC development. As 
      hypoxia induces HIF-1alpha stabilization and adenosine (ado) accumulation, we 
      investigated whether this nucleoside regulates HIF-1alpha in FCs. METHODS AND 
      RESULTS: Ado, under hypoxia, stimulates HIF-1alpha accumulation by activating all 
      adenosine receptors (ARs). HIF-1alpha modulation involved extracellular 
      signal-regulated kinase 1/2 (ERK 1/2), p38 mitogen-activated protein kinase (p38 
      MAPK), and protein kinase B (Akt) phosphorylation in the case of A(1), A(2A), 
      A(2B), and ERK 1/2 phosphorylation in the case of A(3) receptors. Ado, through 
      the activation of A(3) and A(2B) receptors, stimulates vascular endothelial 
      growth factor (VEGF) secretion in a HIF-1alpha-dependent way. Furthermore, ado, 
      through the A(2B) subtype, induces an increase of Interleukin-8 (IL-8) secretion 
      in a ERK 1/2, p38, and Akt kinase-dependent but not HIF-1alpha-mediated way. 
      Finally, ado stimulates FC formation, and this effect is strongly reduced by A(3) 
      and A(2B) blockers and by HIF-1alpha silencing. CONCLUSIONS: This study provides 
      the first evidence that A(3,) A(2B), or mixed A(3)/A(2B) antagonists may be 
      useful to block important steps in the atherosclerotic plaque development 
      ado-induced.
FAU - Gessi, Stefania
AU  - Gessi S
AD  - Chair of Pharmacology, Faculty of Medicine, University of Ferrara, Department of 
      Clinical and Experimental Medicine, Pharmacology Unit, Via Fossato di Mortara 
      17-19, 44100 Ferrara, Italy.
FAU - Fogli, Eleonora
AU  - Fogli E
FAU - Sacchetto, Valeria
AU  - Sacchetto V
FAU - Merighi, Stefania
AU  - Merighi S
FAU - Varani, Katia
AU  - Varani K
FAU - Preti, Delia
AU  - Preti D
FAU - Leung, Edward
AU  - Leung E
FAU - Maclennan, Stephen
AU  - Maclennan S
FAU - Borea, Pier Andrea
AU  - Borea PA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091015
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Azo Compounds)
RN  - 0 (Coloring Agents)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Adenosine A1)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 0 (Receptor, Adenosine A2B)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - G7S71FND9B (oil red O)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*metabolism
MH  - Atherosclerosis/metabolism/pathology
MH  - Azo Compounds
MH  - Coloring Agents
MH  - Foam Cells/cytology/*metabolism
MH  - Humans
MH  - Hypoxia/*metabolism/pathology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Interleukin-8/*metabolism
MH  - Lipoproteins, LDL/metabolism
MH  - MAP Kinase Signaling System/physiology
MH  - Macrophages/cytology/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptor, Adenosine A1/genetics/metabolism
MH  - Receptor, Adenosine A2A/genetics/metabolism
MH  - Receptor, Adenosine A2B/genetics/metabolism
MH  - U937 Cells
MH  - Vascular Endothelial Growth Factor A/*metabolism
EDAT- 2009/10/17 06:00
MHDA- 2010/01/15 06:00
CRDT- 2009/10/17 06:00
PHST- 2009/10/17 06:00 [entrez]
PHST- 2009/10/17 06:00 [pubmed]
PHST- 2010/01/15 06:00 [medline]
AID - ATVBAHA.109.194902 [pii]
AID - 10.1161/ATVBAHA.109.194902 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2010 Jan;30(1):90-7. doi: 
      10.1161/ATVBAHA.109.194902. Epub 2009 Oct 15.