PMID- 19013509
OWN - NLM
STAT- MEDLINE
DCOM- 20090220
LR  - 20211020
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Print)
IS  - 0378-1119 (Linking)
VI  - 430
IP  - 1-2
DP  - 2009 Feb 1
TI  - Sildenafil augments early protective transcriptional changes after ischemia in 
      mouse myocardium.
PG  - 30-7
LID - 10.1016/j.gene.2008.10.009 [doi]
AB  - Recently, targeting cyclic-GMP specific phosphodiesterase-5 (PDE5) has attracted 
      much interest in several cardiopulmonary diseases, in particular myocardial 
      ischemia (MI). Although multiple mechanisms were postulated for these beneficial 
      effects at cellular level, early transcriptional changes were unknown. The aim of 
      present study was to examine gene expression profiles in response to MI after 24 
      h of ischemia in murine model and compare transcriptional modulation by 
      sildenafil, a popular phosphodiesterase 5 (PDE5) inhibitor. Mice were divided 
      into four groups: Control sham (C), Sildenafil sham (S), Control MI (CMI) and 
      Sildenafil MI (SMI). Sildenafil was given at a dose of 0.7 mg/kg 
      intraperitoneally 30 min before LAD occlusion. cDNA microarray analysis of 
      peri-infarct tissue was done using a custom cloneset and employing a looped dye 
      swap design. Replicate signals were median averaged and normalized using LOWESS 
      algorithm. R/MAANOVA analysis was used and false discovery rate corrected 
      permutation p-values <0.005 were employed as significance thresholds. 156 genes 
      were identified as significantly regulated demonstrating fold difference >1.5 in 
      at least one of the four groups. 52 genes were significantly upregulated in SMI 
      compared to CMI. For a randomly chosen subset of genes (9), microarray data were 
      confirmed through real time RT-PCR. The differentially expressed genes could be 
      classified into following groups based on their function: 
      phosphorylation/dephosphorylation, apoptosis, differentiation, ATP binding. Our 
      results suggest that sildenafil treatment might regulate early genetic 
      reprogramming strategy for preservation of the ischemic myocardium.
FAU - Vidavalur, Ramesh
AU  - Vidavalur R
AD  - Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, 
      University of Connecticut Health Center; 263 Farmington Avenue, Farmington, CT 
      06030-1110, USA.
FAU - Penumathsa, Suresh Varma
AU  - Penumathsa SV
FAU - Thirunavukkarasu, Mahesh
AU  - Thirunavukkarasu M
FAU - Zhan, Lijun
AU  - Zhan L
FAU - Krueger, Winfried
AU  - Krueger W
FAU - Maulik, Nilanjana
AU  - Maulik N
LA  - eng
GR  - HL 69910/HL/NHLBI NIH HHS/United States
GR  - R01 HL069910/HL/NHLBI NIH HHS/United States
GR  - R01 HL056803-10/HL/NHLBI NIH HHS/United States
GR  - R01 HL069910-05/HL/NHLBI NIH HHS/United States
GR  - HL 56803/HL/NHLBI NIH HHS/United States
GR  - R29 HL056803/HL/NHLBI NIH HHS/United States
GR  - R01 HL056803/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081025
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (Piperazines)
RN  - 0 (Purines)
RN  - 0 (Sulfones)
RN  - BW9B0ZE037 (Sildenafil Citrate)
SB  - IM
MH  - Animals
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardial Ischemia/*genetics/*prevention & control
MH  - Myocardium/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Piperazines/*pharmacology
MH  - Purines/pharmacology
MH  - Reproducibility of Results
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sildenafil Citrate
MH  - Sulfones/*pharmacology
MH  - Transcription, Genetic/*drug effects
PMC - PMC2650511
MID - NIHMS90451
EDAT- 2008/11/18 09:00
MHDA- 2009/02/21 09:00
PMCR- 2010/02/01
CRDT- 2008/11/18 09:00
PHST- 2008/08/14 00:00 [received]
PHST- 2008/10/01 00:00 [revised]
PHST- 2008/10/02 00:00 [accepted]
PHST- 2008/11/18 09:00 [pubmed]
PHST- 2009/02/21 09:00 [medline]
PHST- 2008/11/18 09:00 [entrez]
PHST- 2010/02/01 00:00 [pmc-release]
AID - S0378-1119(08)00532-5 [pii]
AID - 10.1016/j.gene.2008.10.009 [doi]
PST - ppublish
SO  - Gene. 2009 Feb 1;430(1-2):30-7. doi: 10.1016/j.gene.2008.10.009. Epub 2008 Oct 
      25.