PMID- 12865503
OWN - NLM
STAT- MEDLINE
DCOM- 20040827
LR  - 20071115
IS  - 1531-2267 (Electronic)
IS  - 1094-8341 (Linking)
VI  - 15
IP  - 2
DP  - 2003 Oct 17
TI  - Differential myocardial gene expression in the development and rescue of murine 
      heart failure.
PG  - 105-14
AB  - Numerous murine models of heart failure (HF) have been described, many of which 
      develop progressive deterioration of cardiac function. We have recently 
      demonstrated that several of these can be "rescued" or prevented by transgenic 
      cardiac expression of a peptide inhibitor of the beta-adrenergic receptor kinase 
      (betaARKct). To uncover genomic changes associated with cardiomyopathy and/or its 
      phenotypic rescue by the betaARKct, oligonucleotide microarray analysis of left 
      ventricular (LV) gene expression was performed in a total of 53 samples, 
      including 12 each of Normal, HF, and Rescue. Multiple statistical analyses 
      demonstrated significant differences between all groups and further demonstrated 
      that betaARKct Rescue returned gene expression toward that of Normal. In our 
      statistical analyses, we found that the HF phenotype is blindly predictable based 
      solely on gene expression profile. To investigate the progression of HF, LV gene 
      expression was determined in young mice with mildly diminished cardiac function 
      and in older mice with severely impaired cardiac function. Interestingly, mild 
      and advanced HF mice shared similar gene expression profiles, and importantly, 
      the mild HF mice were predicted as having a HF phenotype when blindly subjected 
      to our predictive model described above. These data not only validate our 
      predictive model but further demonstrate that, in these mice, the HF gene 
      expression profile appears to already be set in the early stages of HF 
      progression. Thus we have identified methodologies that have the potential to be 
      used for predictive genomic profiling of cardiac phenotype, including 
      cardiovascular disease.
FAU - Blaxall, Burns C
AU  - Blaxall BC
AD  - Department of Surgery, Duke University Medical Center, Durham, North Carolina 
      27710 , USA.
FAU - Spang, Rainer
AU  - Spang R
FAU - Rockman, Howard A
AU  - Rockman HA
FAU - Koch, Walter J
AU  - Koch WJ
LA  - eng
GR  - HL-65184/HL/NHLBI NIH HHS/United States
GR  - R01-HL-61690/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031017
PL  - United States
TA  - Physiol Genomics
JT  - Physiological genomics
JID - 9815683
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.15 (beta-Adrenergic Receptor Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Cardiac Output, Low/*genetics/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/genetics
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - *Gene Expression
MH  - Gene Expression Profiling
MH  - Heart Ventricles/*metabolism
MH  - Mice
MH  - Oligonucleotide Array Sequence Analysis
MH  - Regression Analysis
MH  - beta-Adrenergic Receptor Kinases
EDAT- 2003/07/17 05:00
MHDA- 2004/08/28 05:00
CRDT- 2003/07/17 05:00
PHST- 2003/07/17 05:00 [pubmed]
PHST- 2004/08/28 05:00 [medline]
PHST- 2003/07/17 05:00 [entrez]
AID - 00087.2003 [pii]
AID - 10.1152/physiolgenomics.00087.2003 [doi]
PST - epublish
SO  - Physiol Genomics. 2003 Oct 17;15(2):105-14. doi: 
      10.1152/physiolgenomics.00087.2003.