Document Detail


Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload.
MedLine Citation:
PMID:  16567591     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cardiac hypertrophy is associated with upregulation of vascular endothelial growth factor (VEGF) in the myocardium. Here, we evaluated the effects of a decoy VEGF receptor on heart morphology and function to a murine model of pressure overload hypertrophy. Mice were administered adenoviral vector encoding a decoy VEGF receptor (Ad-Flk), and their hearts were subjected to pressure overload by transverse aortic constriction (TAC). Treatment with Ad-Flk led to a net reduction in capillary density in hearts subjected to TAC. Ad-Flk also led to a reduction in TAC-induced cardiac hypertrophy and promoted left ventricle dilatation and a loss in contractile function. Treatment with Ad-Flk markedly increased myocardial fibrosis and collagen gene upregulation. In contrast, Ad-Flk had no effect on any of these parameters in sham-treated mice. Administration of a VEGF trap reagent diminished pressure overload cardiac hypertrophy and promoted the progression to heart failure but had no effect on sham-treated animals. These findings suggest that VEGF is required to maintain myocardial capillary density and that reductions in the vascular bed are associated with the transition from compensatory hypertrophy to failure.
Authors:
Yasuhiro Izumiya; Ichiro Shiojima; Kaori Sato; Douglas B Sawyer; Wilson S Colucci; Kenneth Walsh
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-03-27
Journal Detail:
Title:  Hypertension     Volume:  47     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-21     Completed Date:  2006-05-03     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  887-93     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological*
Animals
Aorta
Capillaries / pathology
Cardiac Output, Low / etiology*
Cardiomegaly / complications*,  etiology,  pathology,  physiopathology
Collagen / metabolism
Constriction
Coronary Circulation
Echocardiography
Fibrosis
Gene Transfer Techniques
Hypertension / complications*,  physiopathology
Immunoglobulin Fc Fragments / genetics
Male
Mice
Mice, Inbred C57BL
Myocardial Contraction
Myocardium / metabolism,  pathology
Up-Regulation
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-2 / genetics,  metabolism
Ventricular Remodeling
Grant Support
ID/Acronym/Agency:
AG15052/AG/NIA NIH HHS; AR40197/AR/NIAMS NIH HHS; HL66957/HL/NHLBI NIH HHS; HL77774/HL/NHLBI NIH HHS; R01 AG015052/AG/NIA NIH HHS; R01 AG015052-04/AG/NIA NIH HHS; R01 HL077774/HL/NHLBI NIH HHS; R01 HL077774-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Immunoglobulin Fc Fragments; 0/Vascular Endothelial Growth Factor A; 9007-34-5/Collagen; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2
Comments/Corrections
Comment In:
Hypertension. 2006 May;47(5):827-9   [PMID:  16567590 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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