PMID- 21403100
OWN - NLM
STAT- MEDLINE
DCOM- 20110531
LR  - 20220410
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 123
IP  - 12
DP  - 2011 Mar 29
TI  - Long-term cardiac pro-B-type natriuretic peptide gene delivery prevents the 
      development of hypertensive heart disease in spontaneously hypertensive rats.
PG  - 1297-305
LID - 10.1161/CIRCULATIONAHA.110.981720 [doi]
AB  - 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.
FAU - Cataliotti, Alessandro
AU  - Cataliotti A
AD  - Molecular Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. 
      ikeda.yasuhiro@mayo.edu
FAU - Tonne, Jason M
AU  - Tonne JM
FAU - Bellavia, Diego
AU  - Bellavia D
FAU - Martin, Fernando L
AU  - Martin FL
FAU - Oehler, Elise A
AU  - Oehler EA
FAU - Harders, Gerald E
AU  - Harders GE
FAU - Campbell, Jarryd M
AU  - Campbell JM
FAU - Peng, Kaw-Whye
AU  - Peng KW
FAU - Russell, Stephen J
AU  - Russell SJ
FAU - Malatino, Lorenzo S
AU  - Malatino LS
FAU - Burnett, John C Jr
AU  - Burnett JC Jr
FAU - Ikeda, Yasuhiro
AU  - Ikeda Y
LA  - eng
GR  - R01 HL036634-24/HL/NHLBI NIH HHS/United States
GR  - P01 HL076611-04/HL/NHLBI NIH HHS/United States
GR  - R01 HL036634/HL/NHLBI NIH HHS/United States
GR  - R01 HL098502/HL/NHLBI NIH HHS/United States
GR  - R01 HL36634/HL/NHLBI NIH HHS/United States
GR  - P01 HL076611/HL/NHLBI NIH HHS/United States
GR  - P01 HL76611/HL/NHLBI NIH HHS/United States
GR  - R01 HL098502-01A1/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110314
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Precursors)
RN  - 0 (brain-derived neurotrophic factor precursor)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Blood Pressure/genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Echocardiography
MH  - Genetic Therapy/*methods
MH  - Heart Failure/diagnostic imaging/genetics/*prevention & control
MH  - Hypertension/genetics/*therapy
MH  - Plasmids/genetics
MH  - Protein Precursors/*genetics
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Wistar
MH  - Ventricular Remodeling/genetics
PMC - PMC3081597
MID - NIHMS278591
EDAT- 2011/03/16 06:00
MHDA- 2011/06/01 06:00
PMCR- 2012/03/29
CRDT- 2011/03/16 06:00
PHST- 2011/03/16 06:00 [entrez]
PHST- 2011/03/16 06:00 [pubmed]
PHST- 2011/06/01 06:00 [medline]
PHST- 2012/03/29 00:00 [pmc-release]
AID - CIRCULATIONAHA.110.981720 [pii]
AID - 10.1161/CIRCULATIONAHA.110.981720 [doi]
PST - ppublish
SO  - Circulation. 2011 Mar 29;123(12):1297-305. doi: 
      10.1161/CIRCULATIONAHA.110.981720. Epub 2011 Mar 14.