Influência do background genético na angiogênese inflamatória sob a influência do dipiridamol

Abstract

Inflammation and angiogenesis, key components of fibrovascular tissue growth, a biological event underlying both physiological (wound healing) and pathological conditions (tumor development, chronic inflammation) exhibit considerable variability among species and strains. We investigated whether the response of inbred and outbred mice strains to dipyridamole (DIP) on these processes would present similar variability. The effects of the drug on blood vessel formation, inflammatory cell recruitment, collagen deposition and cytokine product ion were determined on the fibroproliferative tissue induced by sponge implant in Swiss and Balb/c mice. Angiogenesis as assessed by hemoglobin-Hb and vascular endothelial growth factor-VEGF levels differed between the strains. Swiss implants had the highest hemoglobin content but the lowest VEGF levels. Systemic dipyridamole treatment exerted anti-angiogenic effect on Balb/c implants but pro-angiogenic effect on Swiss implant. The inflammatory enzyme activities myeloperoxidase-MPO (6-fold higher in Balb/c implants) and NAG were reduced by the treatment in Balb/c implants only. Nitrite levels were also higher in Balb/c implants 40% after DIP treatment. TNF- levels were similar in the implants of both strains and were not reduced by DIP. Transforming growth factor -1 (TGF-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. Dipyridamole 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 dipyridamole may provide some answers to clinical evidence for resistance to angiogenic therapy.