Di (2-ethylhexyl) phthalate promotes abdominal aortic aneurysm in mice

The widespread use of plasticizers like di-(2-ethylhexyl) phthalate (DEHP) has led to environmental and health concerns. Recent studies have revealed a positive association between DEHP exposure and cardiovascular disease. However, the relationship between DEHP exposure and abdominal aortic aneurysm (AAA) remains poorly understood. To address this bottleneck, C57BL/6J male mice were utilized to establish a murine CaCl2-induced AAA model, followed by an oral gavage administration of 50 and 250 mg/kg DEHP for 4 weeks. It has been found that DEHP could significantly increase the maximal abdominal aortic diameter and promote vascular inflammation and elastin degradation. Overall, we demonstrate that DEHP aggravates AAA formation by promoting macrophages M1 polarization and VSMCs phenotypic switching. The present study expands the understanding of the toxic effects and molecular mechanisms of DEHP, providing a new perspective for in-depth cardiovascular toxicity exploration of similar compounds.

邻苯二甲酸二(2-乙基己基)酯（di-(2-ethylhexyl) phthalate, DEHP）等塑化剂的广泛应用，已引发环境与健康领域的广泛担忧。现有研究表明，DEHP暴露与心血管疾病存在正相关关联，但DEHP暴露与腹主动脉瘤（abdominal aortic aneurysm, AAA）之间的潜在关联及机制仍有待阐明。为破解这一研究瓶颈，本研究选用C57BL/6J雄性小鼠，构建氯化钙（CaCl2）诱导的小鼠腹主动脉瘤模型，随后分别以50 mg/kg、250 mg/kg的DEHP进行为期4周的灌胃给药。实验结果显示，DEHP可显著增大腹主动脉最大直径，促进血管炎症反应与弹性蛋白降解。综上，本研究证实DEHP可通过促进巨噬细胞M1极化以及血管平滑肌细胞（vascular smooth muscle cells, VSMCs）表型转化，加重腹主动脉瘤的形成。本研究拓展了对DEHP毒性效应与分子机制的认知，为同类化合物的心血管毒性深入探索提供了全新视角。