PMID- 24095869
OWN - NLM
STAT- MEDLINE
DCOM- 20140826
LR  - 20131220
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 101
IP  - 1
DP  - 2014 Jan 1
TI  - Hypoxia-inducible factor 1-induced G protein-coupled receptor 35 expression is an 
      early marker of progressive cardiac remodelling.
PG  - 69-77
LID - 10.1093/cvr/cvt226 [doi]
AB  - AIMS: G protein-coupled receptor 35 (GPR35) has been characterized to be one of 
      the genes that are up-regulated in human heart failure. Since mechanisms 
      controlling GPR35 expression are not known, we investigated the regulation of 
      GPR35 gene and protein expression in cardiac myocytes and in the mouse models of 
      cardiac failure. METHODS AND RESULTS: In cardiac myocytes, GPR35 gene expression 
      was found to be exceptionally sensitive to hypoxia and induced by 
      hypoxia-inducible factor-1 (HIF-1) activation. HIF-1-dependent regulation was 
      established by genetic (HIF-1/VP16, Inhibitory Per/Arnt/Sim domain protein) and 
      chemical [desferrioxamine (DFO)] modulation of the HIF-1 pathway and further 
      confirmed by mutation analysis of the GPR35 promoter and by demonstrating direct 
      binding of endogenous HIF-1 to the gene promoter. Hypoxia increased the number 
      and density of GPR35 receptors on the cardiomyocyte cell membranes. Chemical 
      GPR35 agonist Zaprinast caused GPR35 activation and receptor internalization in 
      cardiac myocytes. In addition, overexpressed GPR35 disrupted actin cytoskeleton 
      arrangement and caused morphological changes in cultured cardiomyocytes. GPR35 
      gene and protein expressions were also induced in mouse models of cardiac 
      failure; the acute phase of myocardial infarction and during the compensatory and 
      decompensatory phase of pressure-load induced cardiac hypertrophy. CONCLUSIONS: 
      Cardiac expression of GPR35 is regulated by hypoxia through activation of HIF-1. 
      The expression of GPR35 in mouse models of cardiac infarction and pressure load 
      suggests that GPR35 could be used as an early marker of progressive cardiac 
      failure.
FAU - Ronkainen, Veli-Pekka
AU  - Ronkainen VP
AD  - Department of Physiology, Institute of Biomedicine and Biocenter Oulu, University 
      of Oulu, FI-90014, Oulu, Finland.
FAU - Tuomainen, Tomi
AU  - Tuomainen T
FAU - Huusko, Jenni
AU  - Huusko J
FAU - Laidinen, Svetlana
AU  - Laidinen S
FAU - Malinen, Marjo
AU  - Malinen M
FAU - Palvimo, Jorma J
AU  - Palvimo JJ
FAU - Yla-Herttuala, Seppo
AU  - Yla-Herttuala S
FAU - Vuolteenaho, Olli
AU  - Vuolteenaho O
FAU - Tavi, Pasi
AU  - Tavi P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131004
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (GPR35 protein, mouse)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Ligands)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cells, Cultured
MH  - *Gene Expression Regulation
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Ligands
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocytes, Cardiac/*metabolism
MH  - Oxygen/*physiology
MH  - Promoter Regions, Genetic
MH  - Receptors, G-Protein-Coupled/*metabolism
MH  - Ventricular Remodeling
OTO - NOTNLM
OT  - GPR35
OT  - HIF-1
OT  - Infarction
OT  - Pressure overload
OT  - Transcription
EDAT- 2013/10/08 06:00
MHDA- 2014/08/27 06:00
CRDT- 2013/10/08 06:00
PHST- 2013/10/08 06:00 [entrez]
PHST- 2013/10/08 06:00 [pubmed]
PHST- 2014/08/27 06:00 [medline]
AID - cvt226 [pii]
AID - 10.1093/cvr/cvt226 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2014 Jan 1;101(1):69-77. doi: 10.1093/cvr/cvt226. Epub 2013 Oct 
      4.