Metformin inhibits inflammatory angiogenesis in a murine sponge model.
To investigate the effects of metformin on angiogenesis, on inflammatory cell accumulation and on production of endogenous cytokines in sponge implant in mice. Polyester-polyurethane sponges were implanted in Swiss mice and metformin (40 or 400mg/kg/day) was given orally for six days. The implants collected at day 7 postimplantation were processed for the assessment of hemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) e collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Metformin treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of transforming growth factor (TGF-beta1) intraimplant. A regulatory function of metformin on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of metformin.
Xavier
D O
DO
FUMEC University, Physiology, Rua da Paisagem 240, Bairro Vila da Serra, Nova Lima, Minas Gerais, Brazil.
Amaral
L S
LS
Gomes
M A
MA
Rocha
M A
MA
Campos
P R
PR
Cota
B D C V
BD
Tafuri
L S A
LS
Paiva
A M R
AM
Silva
J H
JH
Andrade
S P
SP
Belo
A V
AV
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D005549:Foreign-Body Reaction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009195:Peroxidase / Q000032:analysis; D015503:Surgical Sponges; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003094:Collagen; D008687:Metformin; D009195:Peroxidase