PMID- 24259499
OWN - NLM
STAT- MEDLINE
DCOM- 20140929
LR  - 20140121
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 101
IP  - 2
DP  - 2014 Feb 1
TI  - Glyoxalase-1 overexpression in bone marrow cells reverses defective 
      neovascularization in STZ-induced diabetic mice.
PG  - 306-16
LID - 10.1093/cvr/cvt259 [doi]
AB  - AIMS: Methylglyoxal (MG) accumulates in diabetes and impairs neovascularization. 
      This study assessed whether overexpressing the MG-metabolizing enzyme 
      glyoxalase-1 (GLO1) in only bone marrow cells (BMCs) could restore 
      neovascularization in ischaemic tissue of streptozotocin-induced diabetic mice. 
      METHODS AND RESULTS: After 24 h of hyperglycaemic and hypoxic culture, BMCs from 
      GLO1 overexpressing and wild-type (WT) diabetic mice were compared for migratory 
      potential, viability, and mRNA expression of anti-apoptotic genes (Bcl-2 and 
      Bcl-XL). In vivo, BMCs from enhanced green fluorescent protein (eGFP) mice that 
      overexpress GLO1 were used to reconstitute the BM of diabetic mice 
      (GLO1-diabetics). Diabetic and non-diabetic recipients of WT GFP(+) BM served as 
      controls (WT-diabetics and non-diabetics, respectively). Following hindlimb 
      ischaemia, the mobilization of BMCs was measured by flow cytometry. In hindlimbs, 
      the presence of BM-derived angiogenic (GFP(+)CXCR4(+)) and endothelial 
      (GFP(+)vWF(+)) cells and also arteriole density were determined by 
      immunohistochemistry. Hindlimb perfusion was measured using laser Doppler. 
      GLO1-BMCs had superior migratory potential, increased viability, and greater 
      Bcl-2 and Bcl-XL expression, compared with WT BMCs. In vivo, the mobilization of 
      pro-angiogenic BMCs (CXCR4(+), c-kit(+), and Flk(+)) was enhanced post-ischaemia 
      in GLO1-diabetics compared to WT-diabetics. A greater number of GFP(+)CXCR4(+) 
      and GFP(+)vWF(+) BMCs incorporated into the hindlimb tissue of GLO1-diabetics and 
      non-diabetics than in WT-diabetics. Arteriole and capillary density and perfusion 
      were also greater in GLO1-diabetics and non-diabetics. CONCLUSION: This study 
      demonstrates that protection from MG uniquely in BM is sufficient to restore BMC 
      function and neovascularization of ischaemic tissue in diabetes and identifies 
      GLO1 as a potential therapeutic target.
FAU - Vulesevic, Branka
AU  - Vulesevic B
AD  - Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin 
      Street, Ottawa, ON, Canada K1Y 4W7.
FAU - McNeill, Brian
AU  - McNeill B
FAU - Geoffrion, Michele
AU  - Geoffrion M
FAU - Kuraitis, Drew
AU  - Kuraitis D
FAU - McBane, Joanne E
AU  - McBane JE
FAU - Lochhead, Marina
AU  - Lochhead M
FAU - Vanderhyden, Barbara C
AU  - Vanderhyden BC
FAU - Korbutt, Gregory S
AU  - Korbutt GS
FAU - Milne, Ross W
AU  - Milne RW
FAU - Suuronen, Erik J
AU  - Suuronen EJ
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131120
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Angiogenic Proteins)
RN  - 0 (Blood Glucose)
RN  - 0 (Cytokines)
RN  - 722KLD7415 (Pyruvaldehyde)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, mouse)
RN  - EC 4.4.1.5 (Lactoylglutathione Lyase)
SB  - IM
MH  - Angiogenic Proteins/genetics/metabolism
MH  - Animals
MH  - Apoptosis
MH  - Blood Glucose/metabolism
MH  - Bone Marrow Cells/*enzymology
MH  - *Bone Marrow Transplantation
MH  - Cell Movement
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Diabetes Mellitus, Experimental/enzymology/genetics/physiopathology/*surgery
MH  - Diabetes Mellitus, Type 1/enzymology/genetics/physiopathology/*surgery
MH  - Diabetic Angiopathies/enzymology/genetics/physiopathology/*surgery
MH  - Hindlimb
MH  - Humans
MH  - Ischemia/enzymology/genetics/physiopathology/*surgery
MH  - Lactoylglutathione Lyase/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Muscle, Skeletal/*blood supply/pathology
MH  - *Neovascularization, Pathologic
MH  - Nitric Oxide Synthase Type III/genetics/metabolism
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Pyruvaldehyde/metabolism
MH  - Recovery of Function
MH  - Regional Blood Flow
MH  - Time Factors
MH  - Up-Regulation
OTO - NOTNLM
OT  - Bone marrow cells
OT  - Methylglyoxal
OT  - Neovascularization
OT  - Type 1 diabetes
EDAT- 2013/11/22 06:00
MHDA- 2014/09/30 06:00
CRDT- 2013/11/22 06:00
PHST- 2013/11/22 06:00 [entrez]
PHST- 2013/11/22 06:00 [pubmed]
PHST- 2014/09/30 06:00 [medline]
AID - cvt259 [pii]
AID - 10.1093/cvr/cvt259 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2014 Feb 1;101(2):306-16. doi: 10.1093/cvr/cvt259. Epub 2013 Nov 
      20.