Table_1_Ventricular Fibrosis and Coronary Remodeling Following Short-Term Exposure of Healthy and Malnourished Mice to Bisphenol A.DOCX

Bisphenol-A (BPA) is an endocrine disruptor associated with higher risk of insulin resistance, type 2 diabetes, and cardiovascular diseases especially in susceptible populations. Because malnutrition is a nutritional disorder associated with high cardiovascular risk, we sought to compare the effects of short-term BPA exposure on cardiovascular parameters of healthy and protein-malnourished mice. Postweaned male mice were fed a normo- (control) or low-protein (LP) diet for 8 weeks and then exposed or not to BPA (50 μg kg−1 day−1) for the last 9 days. Systolic blood pressure was higher in BPA or LP groups compared with the control group. However, diastolic blood pressure was enhanced by BPA only in malnourished mice. Left ventricle (LV) end diastolic pressure (EDP), collagen deposition, and CTGF mRNA expression were higher in the control or malnourished mice exposed to BPA than in the respective nonexposed groups. Nevertheless, mice fed LP diet exposed to BPA exhibited higher angiotensinogen and cardiac TGF-β1 mRNA expression than mice treated with LP or BPA alone. Wall:lumen ratio and cross-sectional area of intramyocardial arteries were higher either in the LP or BPA group compared with the control mice. Taken together, our data suggest that short-term BPA exposure results in LV diastolic dysfunction and fibrosis, and intramyocardial arteries inward remodeling, besides potentiate protein malnutrition-induced hypertension and cardiovascular risk.

双酚A（Bisphenol-A, BPA）是一种内分泌干扰物，与胰岛素抵抗、2型糖尿病及心血管疾病的发病风险升高相关，尤其在易感人群中更为显著。鉴于营养不良是一类与心血管高风险相关的营养紊乱性疾病，本研究旨在对比短期双酚A暴露对健康小鼠与蛋白质营养不良小鼠心血管参数的影响。断乳后的雄性小鼠被分为正常蛋白（对照）饮食组与低蛋白（LP）饮食组，喂养8周后，其中一半在最后9天予以双酚A暴露处理（剂量为50 μg·kg⁻¹·d⁻¹），另一半不做暴露处理。与对照组相比，双酚A暴露组与低蛋白饮食组小鼠的收缩压均升高。然而，仅在营养不良小鼠中，双酚A暴露才会导致舒张压升高。与各自未暴露的对照组相比，暴露于双酚A的正常饮食小鼠与营养不良小鼠的左心室（LV）舒张末期压（EDP）、胶原沉积水平及CTGF mRNA表达量均更高。不过，与仅接受低蛋白饮食或仅接受双酚A暴露的小鼠相比，同时接受低蛋白饮食与双酚A暴露的小鼠，其血管紧张素原及心脏TGF-β1 mRNA的表达量更高。与对照组小鼠相比，低蛋白饮食组或双酚A暴露组小鼠的心肌内动脉壁腔比与横截面积均升高。综合以上结果，本研究数据表明，短期双酚A暴露不仅会引发左心室舒张功能障碍、纤维化以及心肌内动脉内向重构，还会加剧蛋白质营养不良诱导的高血压与心血管风险。