Basini Giuseppina, Bussolati Simona, Grolli Stefano, Ramoni Roberto, Grasselli Francesca
Dipartimento di Scienze Medico-Veterinarie, Università degli Studi di Parma, Via del Taglio 10, 43126 Parma, Italy.
Can J Physiol Pharmacol. 2017 Apr;95(4):365-371. doi: 10.1139/cjpp-2016-0180. Epub 2016 Oct 20.
Several studies have demonstrated that the endocrine disruptor bisphenol A (BPA) negatively affects animal and human health. An angiogenic process has been suggested among the events disrupted by this molecule, but the underlying mechanisms have not yet been clarified. The effect of BPA on angiogenesis was investigated by means of a bioassay previously validated in our laboratory. Using immortalized swine aortic endothelial cell line (AOC), the development of new blood vessels through a three-dimensional in vitro angiogenesis assay was evaluated. Subsequently, since vascular endothelial growth factor (VEGF) and nitric oxide (NO) are key players in the regulation of the angiogenic process, the effect of BPA on the production of these molecules by AOC was examined. BPA (10 μmol/L) stimulated AOC growth (p < 0.05) and VEGF production (p < 0.05), but did not modify NO levels. Our data suggest that the endocrine-disrupting effects of BPA could also be associated with the promotion of vascular growth, thus interfering with a physiologically finely tuned process resulting from a delicate balance of numerous molecular processes. The stimulatory effects of BPA on VEGF production may have negative implications, potentially switching the balance toward uncontrolled neovascularization. Moreover, since angiogenesis is involved in several pathologies, including cancer growth and progression, potential health risks of BPA exposure should be carefully monitored.
多项研究表明,内分泌干扰物双酚A(BPA)会对动物和人类健康产生负面影响。在受该分子干扰的诸多事件中,有人提出了血管生成过程,但相关潜在机制尚未阐明。我们通过先前在实验室验证过的生物测定法研究了双酚A对血管生成的影响。使用永生化猪主动脉内皮细胞系(AOC),通过三维体外血管生成测定法评估新血管的生成。随后,鉴于血管内皮生长因子(VEGF)和一氧化氮(NO)是血管生成过程调节中的关键因素,研究了双酚A对AOC产生这些分子的影响。双酚A(10 μmol/L)刺激了AOC的生长(p < 0.05)和VEGF的产生(p < 0.05),但未改变NO水平。我们的数据表明,双酚A的内分泌干扰作用也可能与促进血管生长有关,从而干扰了由众多分子过程的微妙平衡所导致的生理上精细调节的过程。双酚A对VEGF产生的刺激作用可能具有负面影响,有可能使平衡转向不受控制的新血管形成。此外,由于血管生成涉及多种病理过程,包括癌症的生长和进展,因此应仔细监测双酚A暴露的潜在健康风险。