PMID- 25014216
OWN - NLM
STAT- MEDLINE
DCOM- 20150304
LR  - 20240322
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 7
DP  - 2014
TI  - PARP-inhibitor treatment prevents hypertension induced cardiac remodeling by 
      favorable modulation of heat shock proteins, Akt-1/GSK-3beta and several PKC 
      isoforms.
PG  - e102148
LID - 10.1371/journal.pone.0102148 [doi]
LID - e102148
AB  - Spontaneously hypertensive rat (SHR) is a suitable model for studies of the 
      complications of hypertension. It is known that activation of poly(ADP-ribose) 
      polymerase enzyme (PARP) plays an important role in the development of 
      postinfarction as well as long-term hypertension induced heart failure. In this 
      study, we examined whether PARP-inhibitor (L-2286) treatment could prevent the 
      development of hypertensive cardiopathy in SHRs. 6-week-old SHR animals were 
      treated with L-2286 (SHR-L group) or placebo (SHR-C group) for 24 weeks. 
      Wistar-Kyoto rats were used as aged-matched, normotensive controls (WKY group). 
      Echocardiography was performed, brain-derived natriuretic peptide (BNP) activity 
      and blood pressure were determined at the end of the study. We detected the 
      extent of fibrotic areas. The amount of heat-shock proteins (Hsps) and the 
      phosphorylation state of Akt-1(Ser473), glycogen synthase kinase (GSK)-3beta(Ser9), 
      forkhead transcription factor (FKHR)(Ser256), mitogen activated protein kinases 
      (MAPKs), and protein kinase C (PKC) isoenzymes were monitored. The elevated blood 
      pressure in SHRs was not influenced by PARP-inhibitor treatment. Systolic left 
      ventricular function and BNP activity did not differ among the three groups. 
      L-2286 treatment decreased the marked left ventricular (LV) hypertrophy which was 
      developed in SHRs. Interstitial collagen deposition was also decreased by L-2286 
      treatment. The phosphorylation of extracellular signal-regulated kinase 
      (ERK)1/2(Thr183-Tyr185), Akt-1(Ser473), GSK-3beta(Ser9), FKHR(Ser256), and PKC 
      epsilon(Ser729) and the level of Hsp90 were increased, while the activity of PKC 
      alpha/betaII(Thr638/641), zeta/lambda(410/403) were mitigated by L-2286 administration. We could 
      detect signs of LV hypertrophy without congestive heart failure in SHR groups. 
      This alteration was prevented by PARP inhibition. Our results suggest that 
      PARP-inhibitor treatment has protective effect already in the early stage of 
      hypertensive myocardial remodeling.
FAU - Deres, Laszlo
AU  - Deres L
AD  - First Department of Medicine, Division of Cardiology, University of Pecs, Pecs, 
      Hungary; Szentagothai Janos Research Center, University of Pecs, Medical School, 
      Pecs, Hungary.
FAU - Bartha, Eva
AU  - Bartha E
AD  - First Department of Medicine, Division of Cardiology, University of Pecs, Pecs, 
      Hungary.
FAU - Palfi, Anita
AU  - Palfi A
AD  - First Department of Medicine, Division of Cardiology, University of Pecs, Pecs, 
      Hungary.
FAU - Eros, Krisztian
AU  - Eros K
AD  - First Department of Medicine, Division of Cardiology, University of Pecs, Pecs, 
      Hungary; Szentagothai Janos Research Center, University of Pecs, Medical School, 
      Pecs, Hungary.
FAU - Riba, Adam
AU  - Riba A
AD  - First Department of Medicine, Division of Cardiology, University of Pecs, Pecs, 
      Hungary; Szentagothai Janos Research Center, University of Pecs, Medical School, 
      Pecs, Hungary.
FAU - Lantos, Janos
AU  - Lantos J
AD  - Department of Surgical Research and Techniques, University of Pecs, Pecs, 
      Hungary.
FAU - Kalai, Tamas
AU  - Kalai T
AD  - Department of Organic and Medicinal Chemistry, University of Pecs, Pecs, Hungary.
FAU - Hideg, Kalman
AU  - Hideg K
AD  - Department of Organic and Medicinal Chemistry, University of Pecs, Pecs, Hungary.
FAU - Sumegi, Balazs
AU  - Sumegi B
AD  - Szentagothai Janos Research Center, University of Pecs, Medical School, Pecs, 
      Hungary; Department of Biochemistry and Medical Chemistry, Medical School, 
      University of Pecs, Pecs, Hungary; MTA-PTE Nuclear-Mitochondrial Interactions 
      Research Group, Pecs, Hungary.
FAU - Gallyas, Ferenc
AU  - Gallyas F
AD  - Department of Biochemistry and Medical Chemistry, Medical School, University of 
      Pecs, Pecs, Hungary; MTA-PTE Nuclear-Mitochondrial Interactions Research Group, 
      Pecs, Hungary.
FAU - Toth, Kalman
AU  - Toth K
AD  - First Department of Medicine, Division of Cardiology, University of Pecs, Pecs, 
      Hungary.
FAU - Halmosi, Robert
AU  - Halmosi R
AD  - First Department of Medicine, Division of Cardiology, University of Pecs, Pecs, 
      Hungary; Szentagothai Janos Research Center, University of Pecs, Medical School, 
      Pecs, Hungary.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140711
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (2-((2-piperidin-1-ylethyl)thio)quinazolin-4(3H)-one)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Piperidines)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 0 (Quinazolines)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - 0 (Foxo1 protein, rat)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
MH  - Forkhead Transcription Factors/genetics/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Glycogen Synthase Kinase 3/genetics/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - HSP90 Heat-Shock Proteins/genetics/metabolism
MH  - Heart Failure/etiology/genetics/physiopathology/*prevention & control
MH  - Hypertension/complications/*drug therapy/genetics/physiopathology
MH  - Hypertrophy, Left Ventricular/*drug therapy/etiology/genetics/physiopathology
MH  - Isoenzymes/genetics/metabolism
MH  - Male
MH  - Natriuretic Peptide, Brain/genetics/metabolism
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Phosphorylation
MH  - Piperidines/*pharmacology
MH  - *Poly(ADP-ribose) Polymerase Inhibitors
MH  - Poly(ADP-ribose) Polymerases/genetics/metabolism
MH  - Protein Kinase C/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Quinazolines/*pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Signal Transduction
PMC - PMC4094529
COIS- Competing Interests: Co-author Ferenc Gallyas Jr. PhD, DSc is a PLOS ONE 
      Editorial Board member. This does not alter the authors' adherence to PLOS ONE 
      Editorial policies and criteria.
EDAT- 2014/07/12 06:00
MHDA- 2015/03/05 06:00
PMCR- 2014/07/11
CRDT- 2014/07/12 06:00
PHST- 2014/02/21 00:00 [received]
PHST- 2014/06/15 00:00 [accepted]
PHST- 2014/07/12 06:00 [entrez]
PHST- 2014/07/12 06:00 [pubmed]
PHST- 2015/03/05 06:00 [medline]
PHST- 2014/07/11 00:00 [pmc-release]
AID - PONE-D-14-08157 [pii]
AID - 10.1371/journal.pone.0102148 [doi]
PST - epublish
SO  - PLoS One. 2014 Jul 11;9(7):e102148. doi: 10.1371/journal.pone.0102148. 
      eCollection 2014.