title: Genetic background determines inflammatory angiogenesis response to dipyridamole in mice.
abstract: Inflammation and angiogenesis, key components of fibrovascular tissue growth, exhibit considerable variability among species and strains. We investigated whether the response of inbred and outbred mice strains to dipyridamole (DP) on these processes would present similar variability. The effects of the drug on blood vessel formation, inflammatory cell recruitment, collagen deposition and cytokine production were determined on the fibroproliferative tissue induced by sponge implants in Swiss and Balb/c mice. Angiogenesis as assessed by hemoglobin (Hb) and vascular endothelial growth factor (VEGF) concentrations differed between the strains. Swiss implants had the highest Hb content but the lowest VEGF concentrations. Systemic DP treatment exerted an antiangiogenic effect on Balb/c implants but an proangiogenic effect on Swiss implants. The inflammatory enzyme activities myeloperoxidase (six-fold higher in Balb/c implants) and N-acetyl-β-D-glucosaminidase were reduced by the treatment in Balb/c implants only. Nitrite concentrations were also higher in Balb/c implants by 40% after DP treatment. Tumor necrosis factor-alpha levels were similar in the implants of both strains and were not reduced by DP. Transforming growth factor β-1 levels and collagen deposition also varied between the strains. The inbred strain had similar levels of the cytokine but implants of Swiss mice presented more collagen. DP treatment reduced collagen deposition in Balb/c implants only. Our data showing the influence of the genetic background on marked heterogeneity of inflammatory angiogenesis components and differential sensitivity to DP may provide some answers to clinical evidence for resistance to angiogenic therapy.
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Av. Antônio Carlos 6627-Campus Pampulha, Cx Post 468, CEP 31270-901, Belo Horizonte/MG, Brazil.
authors.forename: Fernanda Portella
authors.initials: FP
authors.lastname: Sampaio
authors.forename: Pollyana Ribeiro
authors.initials: PR
authors.lastname: Castro
authors.forename: Suzane Mota
authors.initials: SM
authors.lastname: Marques
authors.forename: Paula Peixoto
authors.initials: PP
authors.lastname: Campos
authors.forename: Mônica Alves Neves Diniz
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Silvia Passos
authors.initials: SP
authors.lastname: Andrade
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity; D003094:Collagen / Q000378:metabolism; D004176:Dipyridamole / Q000378:metabolism / Q000494:pharmacology*; D006454:Hemoglobins / Q000032:analysis; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D009195:Peroxidase / Q000096:biosynthesis / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D013045:Species Specificity; D015503:Surgical Sponges; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042442:Vascular Endothelial Growth Factors / Q000032:analysis
chemical_list: D006454:Hemoglobins; D009573:Nitrites; D010726:Phosphodiesterase Inhibitors; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide; D004176:Dipyridamole; D003094:Collagen; D009195:Peroxidase; D000118:Acetylglucosaminidase