PMID- 21723687
OWN - NLM
STAT- MEDLINE
DCOM- 20111110
LR  - 20220113
IS  - 1097-6809 (Electronic)
IS  - 0741-5214 (Print)
IS  - 0741-5214 (Linking)
VI  - 54
IP  - 3
DP  - 2011 Sep
TI  - Adeno-associated virus serotype 9-mediated overexpression of extracellular 
      superoxide dismutase improves recovery from surgical hind-limb ischemia in BALB/c 
      mice.
PG  - 810-8
LID - 10.1016/j.jvs.2011.03.278 [doi]
AB  - OBJECTIVE: Neovascularization is a physiologic repair process that partly depends 
      on nitric oxide. Extracellular superoxide dismutase (EcSOD) is the major 
      scavenger of superoxide. It is an important regulator of nitric oxide 
      bioavailability and thus protects against vascular dysfunction. We hypothesized 
      that overexpression of EcSOD in skeletal muscle would improve recovery from 
      hind-limb ischemia. METHODS: Adeno-associated virus serotype 9 (AAV9) vectors 
      expressing EcSOD or luciferase (control) from the cytomegalovirus promoter were 
      cross-packaged into AAV9 capsids and injected intramuscularly into the hind-limb 
      muscles (1 x 10(11) viral genomes/limb) of 12-week-old mice. Ischemia was induced 
      after intramuscular injections. Laser Doppler was used to measure limb perfusion 
      on days 0, 7, and 14 after injection. Values were expressed as a ratio relative 
      to the nonischemic limb. EcSOD expression was measured by Western blotting. 
      Capillary density was documented by immunohistochemical staining for platelet 
      endothelial cell adhesion molecule. Apoptosis was assessed by terminal 
      deoxynucleotide transferase-mediated biotin-deoxy uridine triphosphate nick-end 
      labeling and necrosis was visually evaluated daily. RESULTS: EcSOD expression was 
      twofold upregulated in EcSOD treated vs control ischemic muscles at day 14. 
      Capillary density (capillaries/fiber) was 1.9-fold higher in treated (1.65 +/- 
      0.02) vs control muscle (0.78 +/- 0.17, P < .05). Recovery of perfusion ratio at 
      day 14 after ischemia was 1.5-fold greater in EcSOD vs control mice (P < .05). 
      The percentage of apoptotic nuclei was 1.3% +/- 0.4% in EcSOD-treated mice compared 
      with 4.2% +/- 0.2% in controls (P < .001). Limb necrosis was also significantly 
      lower in EcSOD vs control mice. CONCLUSION: AAV9-mediated overexpression of EcSOD 
      in skeletal muscle significantly improves recovery from hind-limb ischemia in 
      mice, consistent with improved capillary density and perfusion ratios in treated 
      mice.
CI  - Copyright (c) 2011 Society for Vascular Surgery. Published by Mosby, Inc. All 
      rights reserved.
FAU - Saqib, Amina
AU  - Saqib A
AD  - Division of Cardiovascular Medicine/Department of Medicine, University of 
      Virginia, Charlottesville, VA 22908, USA.
FAU - Prasad, Konkal-Matt R
AU  - Prasad KM
FAU - Katwal, Arabindra B
AU  - Katwal AB
FAU - Sanders, John M
AU  - Sanders JM
FAU - Lye, R John
AU  - Lye RJ
FAU - French, Brent A
AU  - French BA
FAU - Annex, Brian H
AU  - Annex BH
LA  - eng
GR  - R01 HL058582/HL/NHLBI NIH HHS/United States
GR  - R01 HL058582-06/HL/NHLBI NIH HHS/United States
GR  - R33 HL088286/HL/NHLBI NIH HHS/United States
GR  - R33 HL088286-03/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20110702
PL  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 1.13.12.7 (Luciferases, Firefly)
RN  - EC 1.15.1.1 (Sod3 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Blotting, Western
MH  - Capillaries/enzymology/physiopathology
MH  - Cyclic GMP/metabolism
MH  - Dependovirus/*genetics
MH  - Disease Models, Animal
MH  - *Genetic Therapy
MH  - *Genetic Vectors
MH  - Hindlimb
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Injections, Intramuscular
MH  - Ischemia/enzymology/genetics/pathology/physiopathology/*therapy
MH  - Laser-Doppler Flowmetry
MH  - Luciferases, Firefly/biosynthesis/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Muscle, Skeletal/*blood supply
MH  - Necrosis
MH  - *Neovascularization, Physiologic
MH  - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Recovery of Function
MH  - Regional Blood Flow
MH  - Superoxide Dismutase/*biosynthesis/genetics
MH  - Time Factors
PMC - PMC3166979
MID - NIHMS309951
EDAT- 2011/07/05 06:00
MHDA- 2011/11/11 06:00
PMCR- 2012/09/01
CRDT- 2011/07/05 06:00
PHST- 2011/01/10 00:00 [received]
PHST- 2011/03/22 00:00 [revised]
PHST- 2011/03/25 00:00 [accepted]
PHST- 2011/07/05 06:00 [entrez]
PHST- 2011/07/05 06:00 [pubmed]
PHST- 2011/11/11 06:00 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
AID - S0741-5214(11)00828-7 [pii]
AID - 10.1016/j.jvs.2011.03.278 [doi]
PST - ppublish
SO  - J Vasc Surg. 2011 Sep;54(3):810-8. doi: 10.1016/j.jvs.2011.03.278. Epub 2011 Jul 
      2.