Department of Internal Medicine, En Chu Kong Hospital, New Taipei City 237, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan.
Department of Public Health, Tzu Chi University, Hualian County 970, Taiwan.
Environ Int. 2016 Jul-Aug;92-93:157-64. doi: 10.1016/j.envint.2016.04.006. Epub 2016 Apr 20.
Di-(2-ethylhexyl) phthalate (DEHP) has been used worldwide in various products for many years. In vitro studies have shown that exposure to DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) induces endothelial cell apoptosis. Moreover, exposure to DEHP had been linked to cardiovascular risk factors and cardiovascular diseases in epidemiological studies. Circulating microparticles have been known to be indicators of vascular injury. However, whether DEHP or its metabolites are independently associated with microparticles in humans remains unknown. From 2006 to 2008, we recruited 793 subjects (12-30years) from a population-based sample to participate in this cardiovascular disease prevention examination. Each participant was subjected to interviews and biological sample collection to determine the relationship between concentrations of DEHP metabolites MEHP, mono(ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethly-5-oxoheyl) phthalate in urine and concentrations of endothelial microparticles (CD62E and CD31+/CD42a-), platelet microparticles (CD62P and CD31+/CD42a+), and CD14 in serum. Multiple linear regression analysis revealed that an ln-unit increase in MEHP concentration in urine was positively associated with an increase in serum microparticle counts/μL of 0.132 (±0.016) in CD31+/CD42a- (endothelial apoptosis marker), 0.117 (±0.023) in CD31+/CD42a+ (platelet apoptosis marker), and 0.026 (±0.007) in CD14 (monocyte, macrophage, and neutrophil activation marker). There was no association between DEHP metabolite concentration and CD62E or CD62P. In conclusion, a higher MEHP concentration in urine was associated with an increase in endothelial and platelet microparticles in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to DEHP and atherosclerosis.
邻苯二甲酸二(2-乙基己基)酯(DEHP)多年来在世界范围内的各种产品中被广泛使用。体外研究表明,接触 DEHP 和其代谢物单(2-乙基己基)邻苯二甲酸(MEHP)会诱导内皮细胞凋亡。此外,流行病学研究表明,接触 DEHP 与心血管危险因素和心血管疾病有关。循环微颗粒已被认为是血管损伤的指标。然而,DEHP 或其代谢物是否与人体内的微颗粒独立相关尚不清楚。2006 年至 2008 年,我们从基于人群的样本中招募了 793 名(12-30 岁)受试者参加这项心血管疾病预防检查。每位参与者都接受了访谈和生物样本采集,以确定尿液中 DEHP 代谢物 MEHP、单(乙基-5-羟基己基)邻苯二甲酸和单(2-乙基-5-氧代己基)邻苯二甲酸的浓度与血清中内皮微颗粒(CD62E 和 CD31+/CD42a-)、血小板微颗粒(CD62P 和 CD31+/CD42a+)和 CD14 的浓度之间的关系。多元线性回归分析显示,尿液中 MEHP 浓度每增加一个 ln 单位,与 CD31+/CD42a-(内皮细胞凋亡标志物)中血清微颗粒计数/μL 增加 0.132(±0.016)、CD31+/CD42a+(血小板凋亡标志物)中增加 0.117(±0.023)和 CD14(单核细胞、巨噬细胞和中性粒细胞激活标志物)中增加 0.026(±0.007)呈正相关。DEHP 代谢物浓度与 CD62E 或 CD62P 之间没有关联。总之,在这个青少年和年轻成年人队列中,尿液中 MEHP 浓度较高与内皮细胞和血小板微颗粒的增加有关。需要进一步的研究来阐明接触 DEHP 与动脉粥样硬化之间的因果关系。