| Manuscript # |
H-01046-2008 |
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| Current Revision # | 0 |
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| Other Versions | H-01046-2008R1 H-01046-2008R2 |
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| Submission Date | 30th Sep 08 00:00:00 |
Current Stage | |
| Title | Gene profiling of left ventricle eccentric hypertrophy in aortic regurgitation in rats: rationale for targeting the β-adrenergic and renin-angiotensin systems. |
| Running Title | Gene profiling in volume-overload LV hypertrophy |
| Manuscript Type | Research Article |
| Special Section | None |
| Category | None |
| Corresponding Author | Dr. Jacques Couet (Centre de recherche Institut universitaire de cardiologie et pneumologie de Québec) |
| Contributing Authors | Dr. Serge Champetier , Mrs. Azadeh Bojmehrani , Dr. Jonathan Beaudoin , Mr. Dominic Lachance , Mr. Eric Plante , Mrs. Elise Roussel , Dr. Marie Arsenault |
| Abstract | Aortic valve regurgitation (AR) imposes a severe volume overload to the left ventricle (LV) which results in dilation, eccentric hypertrophy and eventually loss of function. Little is known about the impact of AR on LV gene expression. We therefore conducted a gene expression profiling study in the LV of rats with acute and severe AR. We identified 64 genes that were specifically up-regulated and 29 that were down-regulated out of 21910 genes after 2 weeks. Of the up-regulated genes, a good proportion was related to the extracellular matrix. We subsequently studied a subset of 19 genes by quantitative RT-PCR (qPCR) to see if the modulation seen in the LV after two weeks persisted in the chronic phase (after 6 and 12 months) and found that it did persist. Knowing that the adrenergic and renin-angiotensin systems are over-activated in our animal model we were interested to see if blocking those systems using metoprolol and captopril would alter the expression of some up-regulated LV genes in AR rats. By qPCR we observed that up-regulations of LV mRNA levels encoding for pro-collagens type I and III, fibronectin, atrial natriuretic peptide (ANP), transforming growth factor β2 (TGFβ2) and connective tissue growth factor (CTGF) were totally or partially reversed by a combination of metoprolol (25 mg/kg/d) and captopril (100 mg/kg/d). These observations provide a molecular rationale for a medical strategy aiming these systems in the medical treatment of AR and expand the paradigm in the study of this form of LV volume overload. |
| Associate Editor | Dr. Robert Tomanek |
| Key Words | aortic regurgitation, volume overload, heart hypertrophy, renin-angiotensin system, adrenergic system |
| Decision |
Major Revision / 20th Oct 08 |
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Mandatory Submission Form
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JC
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Author Fees
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By Initialing below, the authors agree to pay page charges ($70 per printed journal page) and applicable color figure fees ($400 per figure) if the manuscript is accepted for publication, unless the manuscript is invited. Page charges became mandatory at APS in 1998. There are no waivers given. Nonmembers pay a fee of $400 per color figure if the color is scientifically necessary; unnecessary color in figures (e.g., color line or bar graphs) is not permitted in the APS journals. If the first or last author is an APS member, the color charges are waived upon proof of current membership. Please provide membership information here if applicable.
Initial Here:
JC
APS Member Name:
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Is this person First or Last Author?:
7/8
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Database Deposition
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Yes
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| Copyright Release Date |
3rd Oct 08 |
