| 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: 2012-04-10 |
Medline Journal Info:
|
Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
|
Languages: eng Pagination: 1297-305 Citation Subset: AIM; IM |
Affiliation:
|
Molecular Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. ikeda.yasuhiro@mayo.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenoviridae
/
genetics Animals Blood Pressure / genetics Brain-Derived Neurotrophic Factor / genetics* Echocardiography Gene 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 HL076611-04/HL/NHLBI NIH HHS; P01 HL76611/HL/NHLBI NIH HHS; R01 HL036634-24/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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Prevention of Ventricular Fibrillation Episodes in Brugada Syndrome by Catheter Ablation Over the An...
Next Document: Fatigue in spinocerebellar ataxia: patient self-assessment of an early and disabling symptom.