PMID- 23089731
OWN - NLM
STAT- MEDLINE
DCOM- 20130509
LR  - 20211021
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 20
IP  - 12
DP  - 2012 Dec
TI  - AAV9-mediated VEGF-B gene transfer improves systolic function in progressive left 
      ventricular hypertrophy.
PG  - 2212-21
LID - 10.1038/mt.2012.145 [doi]
AB  - Mechanisms of the transition from compensatory hypertrophy to heart failure are 
      poorly understood and the roles of vascular endothelial growth factors (VEGFs) in 
      this process have not been fully clarified. We determined the expression profile 
      of VEGFs and relevant receptors during the progression of left ventricular 
      hypertrophy (LVH). C57BL mice were exposed to transversal aortic constriction 
      (TAC) and the outcome was studied at different time points (1 day, 2, 4, and 10 
      weeks). A clear compensatory phase (2 weeks after TAC) was seen with following 
      heart failure (4 weeks after TAC). Interestingly, VEGF-C and VEGF-D as well as 
      VEGF receptor-3 (VEGFR-3) were upregulated in the compensatory hypertrophy and 
      VEGF-B was downregulated in the heart failure. After treatment with 
      adeno-associated virus serotype 9 (AAV9)-VEGF-B(186) gene therapy in the 
      compensatory phase for 4 weeks the function of the heart was preserved due to 
      angiogenesis, inhibition of apoptosis, and promotion of cardiomyocyte 
      proliferation. Also, the genetic programming towards fetal gene expression, a 
      known phenomenon in heart failure, was partly reversed in 
      AAV9-VEGF-B(186)-treated mice. We conclude that VEGF-C and VEGF-D are associated 
      with the compensatory LVH and that AAV9-VEGF-B(186) gene transfer can rescue the 
      function of the failing heart and postpone the transition towards heart failure.
FAU - Huusko, Jenni
AU  - Huusko J
AD  - Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for 
      Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, 
      Kuopio, Finland.
FAU - Lottonen, Line
AU  - Lottonen L
FAU - Merentie, Mari
AU  - Merentie M
FAU - Gurzeler, Erika
AU  - Gurzeler E
FAU - Anisimov, Andrey
AU  - Anisimov A
FAU - Miyanohara, Atsushi
AU  - Miyanohara A
FAU - Alitalo, Kari
AU  - Alitalo K
FAU - Tavi, Pasi
AU  - Tavi P
FAU - Yla-Herttuala, Seppo
AU  - Yla-Herttuala S
LA  - eng
GR  - P01 HL066941/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121023
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Vascular Endothelial Growth Factor B)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Echocardiography
MH  - Hypertrophy, Left Ventricular/physiopathology/*therapy
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Endothelial Growth Factor B/genetics/*metabolism
PMC - PMC3519981
EDAT- 2012/10/24 06:00
MHDA- 2013/05/10 06:00
PMCR- 2013/12/01
CRDT- 2012/10/24 06:00
PHST- 2012/10/24 06:00 [entrez]
PHST- 2012/10/24 06:00 [pubmed]
PHST- 2013/05/10 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - S1525-0016(16)32225-0 [pii]
AID - 10.1038/mt.2012.145 [doi]
PST - ppublish
SO  - Mol Ther. 2012 Dec;20(12):2212-21. doi: 10.1038/mt.2012.145. Epub 2012 Oct 23.