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| Status |
Public on Nov 03, 2005 |
| Title |
Differential regional gene expression from cardiac dyssynchrony |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Right ventricular free wall (RVFW) pacing results in left ventricular dyssynchrony with early septal shortening followed by late lateral contraction that reciprocally stretches the septum. Dyssynchrony is disadvantageous to cardiac mechano-energetics, yet little is known about its molecular consequences. We tested the hypothesis that dyssynchrony selectively alters regional gene expression in mice, employing a novel miniature implantable cardiac pacemaker. Mice were subjected to 1-week overdrive RVFW pacing (720 min-1, baseline HR 520-620 min-1) to induce dyssynchrony (pacemaker: 3V lithium battery, rate programmable, 0.8 grams, bipolar lead). Electrical capture was confirmed by pulsed-wave Doppler at implantation and terminal study, and dyssynchrony by echocardiography. Gene expression from left ventricular septal and lateral-wall myocardium were assessed by microarray (dual-dye method, Agilent) using oligonucleotide probes and dye swap. Identical analysis was applied to 4 synchronously contracting controls. Of 22,000 genes surveyed, only 18 genes displayed significant (p<0.01) differential expression between septal/lateral walls exceeding 1.5-fold relative to any disparities in synchronous controls. These changes were confirmed by qPCR with excellent correlations. Most (16) of the genes showed greater septal expression. Of particular interest were 7 genes coding proteins involved with stretch responses, matrix remodeling, stem cell differentiation to myocyte lineage, and Purkinje fiber differentiation. One-week cardiac dyssynchrony triggers regional differential expression differences in relatively few select genes. Such analysis using a murine implantable pacemaker should facilitate molecular studies of cardiac dyssynchrony and help elucidate novel mechanisms by which stress/stretch stimuli due to dyssynchrony impact the normal and failing heart.
Keywords: Murine cardiac dyssynchrony and differential gene expression, Agilent, microarray, pacing
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| Overall design |
Left ventricle segments from the mouse heart - septal and lateral, were isolated from 4 dyssynchronous mice that were kept separate. RNA from the synchronous mice were pooled into a control septal and lateral sample. Functional genomic analysis was conducted on these 10 RNA samples with fluorophore reversal, such that each sample was assayed on two different microarrays. Corresponding septal and lateral samples from the same heart were paired on the same microarray to measure the relative differences in gene expression between the different regions of the heart then differences were compared across multiple mice to find overlapping genes that were affected by the pacememaker implantation.
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| Contributor(s) |
Bilchick KC, Saha SK, Mikolajczyk E, Cope L, Ferguson WJ, Yu W, Girouard S, Kass DA |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Oct 31, 2005 |
| Last update date |
Dec 06, 2012 |
| Contact name |
Will Ferguson |
| E-mail(s) |
will_ferguson@agilent.com
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| Organization name |
Agilent Technologies
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| Department |
Integrated Biology Solutions
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| Street address |
13017 Wisteria #600
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| City |
Germantown |
| State/province |
MD |
| ZIP/Postal code |
20874 |
| Country |
USA |
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| Platforms (1) |
| GPL891 |
Agilent-011978 Mouse Microarray G4121A (Feature Number version) |
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| Samples (10)
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| GSM81023 |
Gene Expression effects from dyssynchrony - pooled control - dye flip |
| GSM81398 |
Gene Expression effects from dyssynchrony in left ventricle of mouse heart between septal and lateral walls |
| GSM81399 |
Gene Expression effects from dyssynchrony in left ventricle of mouse heart between lateral and septal walls |
| GSM81415 |
Gene Expression effects from dyssynchrony in left ventricle of mouse heart - biological replicate |
| GSM81416 |
Gene Expression effects from dyssynchrony in left ventricle of mouse heart - biological replicate - dye flip |
| GSM81417 |
Gene Expression effects from dyssynchrony in left ventricle of mouse heart - biological replicate 2 |
| GSM81418 |
Gene Expression effects from dyssynchrony in left ventricle of mouse heart - biological replicate2 - dye flip |
| GSM81419 |
Gene Expression effects from dyssynchrony in left ventricle of mouse heart - biological replicate3 |
| GSM81420 |
Gene Expression effects from dyssynchrony in left ventricle of mouse heart - biological replicate3 -dye flip |
| GSM81421 |
Gene Expression effects from dyssynchrony - pooled control |
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| Relations |
| BioProject |
PRJNA93591 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE3535_RAW.tar |
3.3 Mb |
(http)(custom) |
TAR |
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