PMID- 19823587
OWN - NLM
STAT- MEDLINE
DCOM- 20100312
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 10
DP  - 2009 Oct 13
TI  - Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and 
      vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress.
PG  - e7430
LID - 10.1371/journal.pone.0007430 [doi]
LID - e7430
AB  - The aims of this study were to investigate the role of poly(ADP-ribose) 
      polymerase (PARP)-1 in dyslipidemia-associated vascular dysfunction as well as 
      autonomic nervous system dysregulation. Apolipoprotein (ApoE)(-/-) mice fed a 
      high-fat diet were used as a model of atherosclerosis. Vascular and autonomic 
      functions were measured in conscious mice using telemetry. The study revealed 
      that PARP-1 plays an important role in dyslipidemia-associated vascular and 
      autonomic dysfunction. Inhibition of this enzyme by gene knockout partially 
      restored baroreflex sensitivity in ApoE(-/-) mice without affecting baseline 
      heart-rate and arterial pressure, and also improved heart-rate responses 
      following selective blockade of the autonomic nervous system. The protective 
      effect of PARP-1 gene deletion against dyslipidemia-induced endothelial 
      dysfunction was associated with preservation of eNOS activity. Dyslipidemia 
      induced PARP-1 activation was accompanied by oxidative tissue damage, as 
      evidenced by increased expression of iNOS and subsequent protein nitration. 
      PARP-1 gene deletion reversed these effects, suggesting that PARP-1 may 
      contribute to vascular and autonomic pathologies by promoting oxidative tissue 
      injury. Further, inhibition of this oxidative damage may account for protective 
      effects of PARP-1 gene deletion on vascular and autonomic functions. This study 
      demonstrates that PARP-1 participates in dyslipidemia-mediated dysregulation of 
      the autonomic nervous system and that PARP-1 gene deletion normalizes autonomic 
      and vascular dysfunctions. Maintenance of eNOS activity may be associated with 
      the protective effect of PARP-1 gene deletion against dyslipidemia-induced 
      endothelial dysfunction.
FAU - Hans, Chetan P
AU  - Hans CP
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, New Orleans, Louisiana, United States of 
      America.
FAU - Feng, Yumei
AU  - Feng Y
FAU - Naura, Amarjit S
AU  - Naura AS
FAU - Zerfaoui, Mourad
AU  - Zerfaoui M
FAU - Rezk, Bashir M
AU  - Rezk BM
FAU - Xia, Huijing
AU  - Xia H
FAU - Kaye, Alan D
AU  - Kaye AD
FAU - Matrougui, Khalid
AU  - Matrougui K
FAU - Lazartigues, Eric
AU  - Lazartigues E
FAU - Boulares, A Hamid
AU  - Boulares AH
LA  - eng
GR  - P20 RR018766/RR/NCRR NIH HHS/United States
GR  - R01 HL072889/HL/NHLBI NIH HHS/United States
GR  - HL072889/HL/NHLBI NIH HHS/United States
GR  - 1P20RR18766/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091013
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Apolipoproteins E)
RN  - 0 (Dietary Fats)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/*genetics
MH  - Atherosclerosis/*genetics
MH  - Dietary Fats
MH  - Dyslipidemias/*genetics
MH  - Gene Deletion
MH  - Heterozygote
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nitric Oxide Synthase Type III/*genetics
MH  - *Oxidative Stress
MH  - Poly(ADP-ribose) Polymerases/*genetics
PMC - PMC2757717
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/10/14 06:00
MHDA- 2010/03/13 06:00
PMCR- 2009/10/13
CRDT- 2009/10/14 06:00
PHST- 2009/06/26 00:00 [received]
PHST- 2009/09/14 00:00 [accepted]
PHST- 2009/10/14 06:00 [entrez]
PHST- 2009/10/14 06:00 [pubmed]
PHST- 2010/03/13 06:00 [medline]
PHST- 2009/10/13 00:00 [pmc-release]
AID - 09-PONE-RA-11295R1 [pii]
AID - 10.1371/journal.pone.0007430 [doi]
PST - epublish
SO  - PLoS One. 2009 Oct 13;4(10):e7430. doi: 10.1371/journal.pone.0007430.