Document Detail


Onset of experimental severe cardiac fibrosis is mediated by overexpression of Angiotensin-converting enzyme 2.
MedLine Citation:
PMID:  19221212     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-16
Journal Detail:
Title:  Hypertension     Volume:  53     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-20     Completed Date:  2009-04-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  694-700     Citation Subset:  IM    
Affiliation:
BHF GCRC, University of Glasgow, 126 University Place, Glasgow, G12 8TA United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin-Converting Enzyme Inhibitors / 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:
PG/07/015/22372//British Heart Foundation
Chemical
Reg. No./Substance:
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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