Department of General Pathology, Federal University of Minas Gerais, Institute of Biological Sciences, Av. Antônio Carlos 6627 - Campus Pampulha, Cx Post 468, CEP 31270-901, Belo Horizonte, MG, Brazil.
Department of General Pathology, Federal University of Minas Gerais, Institute of Biological Sciences, Av. Antônio Carlos 6627 - Campus Pampulha, Cx Post 468, CEP 31270-901, Belo Horizonte, MG, Brazil.
Biomed Pharmacother. 2017 Feb;86:715-724. doi: 10.1016/j.biopha.2016.11.146. Epub 2017 Jan 5.
Genetic susceptibility is associated with inflammation, neovascularization, and diabetes phenotypes. However, to what extent this susceptibility influences inflammatory angiogenesis in internal injuries in diabetes has not been fully investigated. Using the subcutaneous implantation of a synthetic matrix as an internal wound model in Swiss, C57BL/6 and Balb/c mice, we have studied inflammation, angiogenesis, and cytokine production in the fibrovascular tissue induced by implants in diabetic animals. The hyperglycemic levels (mg/dl) after the diabetogenic treatment were 455.0±15 in Swiss, 393.0±22 in C57BL/6, and 190.0±10 in Balb/c mice. Angiogenesis in Swiss implants from non-diabetic animals were higher than those in the implants from the other strains. However, the angiogenic inducers VEGF and nitric oxide (NO) were higher in implants from non-diabetic Swiss and Balb/c mice. Strain-related differences were also observed in the angiogenic parameters in implants from diabetic mice. Hb content and number of vessels decreased more than 40% in Swiss implants. In contrast, Hb content did not alter in implants from Balb/c diabetic mice and the number of vessels decreased. VEGF levels increased in implants from Swiss and C57BL/6 diabetic mice, but decreased in Balb/c implants. The levels of pro-inflammatory markers intra-implant also varied among the strains in both conditions. In the hyperglycemic environment, almost all inflammatory markers increased in implants from diabetic Swiss mice. These findings demonstrate the major contribution of genetic background in the pattern of inflammatory angiogenesis components of internal injury, in both normoglycemic and hyperglycemic animals.
遗传易感性与炎症、新生血管形成和糖尿病表型有关。然而，这种易感性在多大程度上影响糖尿病内部损伤中的炎症性血管生成尚未得到充分研究。我们使用合成基质的皮下植入作为瑞士、C57BL/6 和 Balb/c 小鼠的内部伤口模型，研究了糖尿病动物植入物诱导的纤维血管组织中的炎症、血管生成和细胞因子产生。糖尿病治疗后，瑞士小鼠的高血糖水平（mg/dl）为 455.0±15，C57BL/6 为 393.0±22，Balb/c 为 190.0±10。来自非糖尿病动物的瑞士植入物中的血管生成高于其他品系的植入物。然而，来自非糖尿病瑞士和 Balb/c 小鼠植入物的血管生成诱导剂 VEGF 和一氧化氮（NO）较高。在糖尿病小鼠植入物中，也观察到与品系相关的血管生成参数差异。瑞士植入物中的 Hb 含量和血管数量减少了 40%以上。相比之下，Balb/c 糖尿病小鼠植入物中的 Hb 含量没有改变，血管数量减少。来自瑞士和 C57BL/6 糖尿病小鼠的植入物中的 VEGF 水平增加，但 Balb/c 植入物中的水平降低。在两种情况下，植入物内的促炎标志物水平在不同品系之间也有所不同。在高血糖环境中，来自糖尿病瑞士小鼠的植入物中的几乎所有炎症标志物都增加。这些发现表明遗传背景在正常血糖和高血糖动物的内部损伤炎症性血管生成成分模式中起主要作用。
