| Onset of experimental severe cardiac fibrosis is mediated by overexpression of Angiotensin-converting enzyme 2. | |
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MedLine Citation:
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PMID: 19221212 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis. |
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Authors:
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Rachel Masson; Stuart A Nicklin; Margaret Anne Craig; Martin McBride; Kirsten Gilday; Paul Gregorevic; James M Allen; Jeffrey S Chamberlain; Godfrey Smith; Delyth Graham; Anna F Dominiczak; Claudio Napoli; Andrew H Baker |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-02-16 |
Journal Detail:
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Title: Hypertension Volume: 53 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-20 Completed Date: 2009-04-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 694-700 Citation Subset: IM |
Affiliation:
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BHF GCRC, University of Glasgow, 126 University Place, Glasgow, G12 8TA United Kingdom. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin-Converting Enzyme Inhibitors
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pharmacology Animals Blood Pressure / drug effects, physiology Disease Models, Animal Enalapril / pharmacology Fibrosis Gene Expression Profiling Gene Expression Regulation, Enzymologic* Gene Transfer Techniques Heart Diseases / genetics*, pathology*, ultrasonography Hypertension / drug therapy, genetics*, pathology* Male Myocytes, Cardiac / pathology Peptidyl-Dipeptidase A / genetics* Polysaccharides Rats Rats, Inbred SHR Severity of Illness Index Transduction, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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PG/07/015/22372//British Heart Foundation |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Polysaccharides; 75847-73-3/Enalapril; 90881-70-2/SHU 454; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.17.-/angiotensin converting enzyme 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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