Document Detail


Long-term cardiac pro-B-type natriuretic peptide gene delivery prevents the development of hypertensive heart disease in spontaneously hypertensive rats.
MedLine Citation:
PMID:  21403100     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Diastolic dysfunction associated with high blood pressure (BP) leads to cardiac remodeling and fibrosis and progression to congestive heart failure. B-type natriuretic peptide (BNP) has BP-lowering, antifibrotic, and antihypertrophic properties, which makes BNP an attractive agent for attenuating the adverse cardiac remodeling associated with hypertension. In the current study, we tested the effects of sustained cardiac proBNP gene delivery on BP, cardiac function, and remodeling in spontaneously hypertensive rats (SHR).
METHODS AND RESULTS: We used the myocardium-tropic adeno-associated virus serotype 9 (AAV9) vector to achieve continuously enhanced cardiac rat proBNP expression. In SHR, a single systemic administration of AAV9 vector allowed long-term cardiac BNP overexpression, resulting in reductions in systolic and diastolic BP for 9 months after injection. Left ventricular (LV) thickness, LV end-systolic dimensions, and LV mass were reduced, whereas ejection fraction was significantly increased, in BNP-treated compared with untreated SHR. Circumferential systolic strain and strain rate of the early phase of diastole were improved in BNP-treated compared with untreated SHR. Noncardiac overexpression of BNP via AAV2 vector was not associated with changes in BP and plasma BNP in SHR. Furthermore, normal Wistar rats injected with AAV9 proBNP vector showed significantly reduced heart weights 4 weeks after injection without BP reduction.
CONCLUSIONS: AAV9 vector facilitates sustained cardiac proBNP overexpression and improves LV function in hypertensive heart disease. Long-term proBNP delivery improved both systolic and diastolic function. The effects on cardiac structure and function occurred independently of BP-lowering effects in normal Wistar rats.
Authors:
Alessandro Cataliotti; Jason M Tonne; Diego Bellavia; Fernando L Martin; Elise A Oehler; Gerald E Harders; Jarryd M Campbell; Kaw-Whye Peng; Stephen J Russell; Lorenzo S Malatino; John C Burnett; Yasuhiro Ikeda
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-14
Journal Detail:
Title:  Circulation     Volume:  123     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-29     Completed Date:  2011-05-31     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1297-305     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Blood Pressure / genetics
Brain-Derived Neurotrophic Factor / genetics*
Echocardiography
Genetic Therapy / methods*
Heart Failure / genetics,  prevention & control*,  ultrasonography
Hypertension / genetics,  therapy*
Plasmids / genetics
Protein Precursors / genetics*
Rats
Rats, Inbred SHR
Rats, Wistar
Ventricular Remodeling / genetics
Grant Support
ID/Acronym/Agency:
P01 HL076611/HL/NHLBI NIH HHS; P01 HL076611-04/HL/NHLBI NIH HHS; P01 HL76611/HL/NHLBI NIH HHS; R01 HL036634/HL/NHLBI NIH HHS; R01 HL036634-24/HL/NHLBI NIH HHS; R01 HL098502/HL/NHLBI NIH HHS; R01 HL098502-01A1/HL/NHLBI NIH HHS; R01 HL098502-01A1/HL/NHLBI NIH HHS; R01 HL098502-03/HL/NHLBI NIH HHS; R01 HL36634/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 0/Protein Precursors; 0/brain-derived neurotrophic factor precursor
Comments/Corrections

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