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| Status |
Public on Jan 15, 2016 |
| Title |
Cardiomyocyte-specific Nitric Oxide Synthase 3 Overexpression in Pressure-Overloaded Left Ventricle. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Aims: Cardiomyocyte-specific nitric oxide synthase 3 (NOS3) overexpression reduces left ventricular (LV) remodelling after myocardial infarction in mice, but its effect on sustained LV pressure-overload remains incompletely understood. We investigated LV structural and functional adaptation to elevated afterload in mice with cardiomyocyte-restricted NOS3 overexpression (NOS3TG) and wild type littermates (WT).
Methods and Results: Hemodynamic indices, cardiac hypertrophy and interstitial fibrosis were measured 10 weeks after transverse aortic constriction (TAC). After 10 weeks TAC, NOS3TG had better preserved systolic function (maximum rates of pressure development normalized to maximal pressure 77±6 versus 65±2 ms-1, P=0.05), reduced heart weight-body weight ratio (HW/BW, 5.0±0.3 versus 5.8±0.1, P<0.05), and cardiomyocyte width than WT (14.9±0.4 vs 16.7±0.2 ?m, P<0.05). After 10 weeks TAC, a 44k cDNA chip-based microarray analysis was validated using real time PCR and revealed significantly altered expression pattern of genes involved in cellular growth, matrix remodelling, and inflammation between genotypes.
Conclusions: Cardiomyocyte-restricted NOS3 overexpression attenuates TAC-induced hypertrophy via autocrine inhibition of cardiomyocyte cell growth, but does not mitigate myocardial fibrosis. The subsequent diastolic dysfunction suggests that inhibition of matrix producing cells during hypertrophic stress is necessary to prevent functional and structural deterioration of the pressure-overloaded heart.
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| Overall design |
Left ventricular mRNA expression profiles were compared between alpha-myosin heavy chain driven nitric oxide synthase 3 (alpha-MHC-NOS3) transgenic and wild type (WT) littermate mice at baseline and 10 weeks after transversal aortic constrcition-induced pressure-overload. Biological repeats: n=4, two males and two females, for each group and condition. Transgenic mice were backcrossed for seven generations (F7) to a C57Bl/6 N background and age and weight matched animals were used for microarray experiments.
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| Contributor(s) |
Pokreisz P, Marsboom G, Vermeersch P, Vandenwijngaert S, Pellens M, Gillijns H, Van Hummelen P, van Eijsden R, Szelid Z, D'Hooge J, Bloch KD, Janssens SP |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Apr 26, 2012 |
| Last update date |
Jan 12, 2017 |
| Contact name |
Rekin's Janky |
| E-mail(s) |
[email protected]
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| Organization name |
VIB
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| Department |
Nucleomics Core
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| Street address |
Herestraat 49 Box 816
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| City |
Leuven |
| ZIP/Postal code |
B-3000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| Samples (16)
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| GSM923064 |
Male alpha-MHC-NOS3 control-intact 4174 |
| GSM923065 |
Female alpha-MHC-NOS3 control-intact 4176 |
| GSM923066 |
Male wild-type littermate control-intact 4178 |
| GSM923067 |
Female wild-type littermate control-intact 4180 |
| GSM923068 |
Male alpha-MHC-NOS3 10 weeks TAC 4182 |
| GSM923069 |
Female alpha-MHC-NOS3 10 weeks TAC 4184 |
| GSM923070 |
Male wild-type littermate 10 weeks TAC 4186 |
| GSM923071 |
Female wild-type littermate 10 weeks TAC 4188 |
| GSM923072 |
Male alpha-MHC-NOS3 10 weeks TAC 4183 |
| GSM923073 |
Female alpha-MHC-NOS3 10 weeks TAC 4185 |
| GSM923074 |
Male wild-type littermate 10 weeks TAC 4187 |
| GSM923075 |
Female wild-type littermate 10 weeks TAC 4189 |
| GSM923076 |
Male alpha-MHC-NOS3 control-intact 4175 |
| GSM923077 |
Female alpha-MHC-NOS3 control-intact 4177 |
| GSM923078 |
Male wild-type littermate control-intact 4179 |
| GSM923079 |
Female wild-type littermate control-intact 4181 |
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| Relations |
| BioProject |
PRJNA162561 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE37597_RAW.tar |
127.6 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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