Influência do background genético na angiogênese inflamatória em camundongos hétero- e isogênicos

Abstract

Inflammation and angiogenesis are key components of fibrovascular tissue growth, a biological event underlying both physiological (wound healing) and pathological conditions (tumor development, chronic inflammation). We investigated these components in three frequently used mouse strains (Swiss, BALB/c and C57BL/6J) to verify the influence of genetic background on the kinetics of inflammatory cell recruitment/activation, neovascularization, extracellular matrix deposition, and cytokine production in polyetherpolyurethane sponge implanted subcutaneously in male mice of these strains. The kinetics of neutrophil recruitment/activation as assessed by myeloperoxidase (MPO) activity was 2 and 3-fold higher in BALB/c implants at day 1 compared with Swiss and C57BL/6J implants, respectively. Macrophage ccumulation/activation as NAG (N-acetyl--D-glucosaminidase) activity was higher in Swiss implants. The levels the monocyte chemoattractant protein 1 (CCL-2) peaked at day 10 in the three types of implants but was produced more by C57BL/6J mice. Angiogenesis (hemoglobin, vascular endothelial growth factor (VEGF), and number of vessels differed among the strains. Swiss implants had the highest hemoglobin content but the lowest VEGF levels. In contrast, BALB/c implants had higher VEGF levels but lower hemoglobin. Collagen deposition and transforming growth factor-1 (TGF-1) levels also varied among the groups. Swiss and BALB/c implants had progressive increase in TGF-1 from 4 to 14 days, while C57BL/6J implants achieved the peak at day 10 and fell at day 14. These findings emphasize the major contribution of genetic background in the temporal pattern and intensity of inflammatory angiogenesis components that may have functional consequences in physiological and pathological conditions where these processes co-exist.