PMID- 25546437
OWN - NLM
STAT- MEDLINE
DCOM- 20150908
LR  - 20201217
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 12
DP  - 2014
TI  - Conditional knockout of prolyl hydroxylase domain protein 2 attenuates high 
      fat-diet-induced cardiac dysfunction in mice.
PG  - e115974
LID - 10.1371/journal.pone.0115974 [doi]
LID - e115974
AB  - Oxygen sensor prolyl hydroxylases (PHDs) play important roles in the regulation 
      of HIF-alpha and cell metabolisms. This study was designed to investigate the direct 
      role of PHD2 in high fat-diet (HFD)-induced cardiac dysfunction. In HFD fed mice, 
      PHD2 expression was increased without significant changes in PHD1 and PHD3 levels 
      in the heart. This was accompanied by a significant upregulation of myeloid 
      differentiation factor 88 (MYD88) and NF-kappaB. To explore the role of PHD2 in 
      HFD-induced cardiac dysfunction, PHD2 conditional knockout mice were fed a HFD 
      for 16 weeks. Intriguingly, knockout of PHD2 significantly reduced MYD88 and 
      NF-kappab expression in HFD mouse hearts. Moreover, knockout of PHD2 inhibited TNFalpha 
      and ICAM-1 expression, and reduced cell apoptosis and macrophage infiltration in 
      HFD mice. This was accompanied by a significant improvement of cardiac function. 
      Most importantly, conditional knockout of PHD2 at late stage in HFD mice 
      significantly improved glucose tolerance and reversed cardiac dysfunction. Our 
      studies demonstrate that PHD2 activity is a critical contributor to the 
      HFD-induced cardiac dysfunction. Inhibition of PHD2 attenuates HFD-induced 
      cardiac dysfunction by a mechanism involving suppression of MYD88/NF-kappab pathway 
      and inflammation.
FAU - Zeng, Heng
AU  - Zeng H
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi, 39216, United States of America.
FAU - Chen, Jian-Xiong
AU  - Chen JX
AD  - Department of Pharmacology and Toxicology, University of Mississippi Medical 
      Center, Jackson, Mississippi, 39216, United States of America.
LA  - eng
GR  - R01 HL102042/HL/NHLBI NIH HHS/United States
GR  - HL102042/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141229
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Angiogenesis Inducing Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Transcription Factor RelA)
RN  - EC 1.14.11.29 (Egln1 protein, mouse)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
SB  - IM
MH  - Angiogenesis Inducing Agents/metabolism
MH  - Animals
MH  - Apoptosis
MH  - Blood Glucose/metabolism
MH  - Body Weight
MH  - Diet, High-Fat/*adverse effects
MH  - Feeding Behavior
MH  - Glucose Tolerance Test
MH  - Heart/*physiopathology
MH  - Heart Function Tests
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases/*deficiency/genetics/*metabolism
MH  - Macrophages/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Obese
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - Transcription Factor RelA/metabolism
MH  - Up-Regulation
PMC - PMC4278833
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/12/30 06:00
MHDA- 2015/09/09 06:00
PMCR- 2014/12/29
CRDT- 2014/12/30 06:00
PHST- 2014/10/01 00:00 [received]
PHST- 2014/11/28 00:00 [accepted]
PHST- 2014/12/30 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/09/09 06:00 [medline]
PHST- 2014/12/29 00:00 [pmc-release]
AID - PONE-D-14-43818 [pii]
AID - 10.1371/journal.pone.0115974 [doi]
PST - epublish
SO  - PLoS One. 2014 Dec 29;9(12):e115974. doi: 10.1371/journal.pone.0115974. 
      eCollection 2014.