Kopf Phillip G, Walker Mary K
University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009 Oct;27(4):276-85. doi: 10.1080/10590500903310195.
The developing cardiovascular system is a sensitive target of many environmental pollutants, including dioxins, dioxin-like polychlorinated biphenyls (PCBs), and some pesticides such as methyl parathion. Laboratory research has utilized a variety of vertebrate models to elucidate potential mechanisms that mediate this cardioteratogenicity and to establish the sensitivity of different species for predicting potential risk to environmental and human health. Studies of dioxin and dioxin-like PCBs have illustrated that piscine, avian, and mammalian embryos exhibit cardiovascular structural changes and functional deficits, although the specific characteristics vary among the individual models. Piscine models typically exhibit reduced blood flow, altered heart looping, and reduced heart size and contraction rate. The chick embryo exhibits extensive cardiac dilation, thinner ventricle walls, and reduced responsiveness to chronotropic stimuli, while the murine embryo exhibits reduced heart size. It is notable that in all models the dioxin-associated cardioteratogenicity is associated with increases in cardiovascular apoptosis and decreases in cardiocyte proliferation. While the cardiotertogenicity in piscine and avian species is associated with overt morbidity and mortality, that is not the case for the murine embryo. However, murine offspring exposed during development to dioxin exhibit cardiac hypertrophy and an increased sensitivity to a second cardiovascular insult in adulthood. Thus, although the mammalian embryo is less sensitive to cardiovascular defects by dioxin and dioxin-like compounds, developmental exposure increases the risk of cardiovascular disease later in life. The impact of developmental exposure to dioxin-like chemicals on human cardiovascular disease susceptibility is not known. However, recent animal research has confirmed human epidemiology studies that dioxin exposure in adulthood is associated with hypertension and cardiovascular disease.
正在发育的心血管系统是许多环境污染物的敏感靶点，这些污染物包括二噁英、二噁英类多氯联苯（PCBs）以及一些农药，如甲基对硫磷。实验室研究利用了多种脊椎动物模型来阐明介导这种心脏致畸性的潜在机制，并确定不同物种对于预测环境和人类健康潜在风险的敏感性。对二噁英和二噁英类多氯联苯的研究表明，鱼类、鸟类和哺乳动物胚胎均表现出心血管结构变化和功能缺陷，尽管各个模型中的具体特征有所不同。鱼类模型通常表现为血流减少、心脏环化改变、心脏大小和收缩率降低。鸡胚表现出广泛的心脏扩张、心室壁变薄以及对变时性刺激的反应性降低，而鼠胚则表现为心脏变小。值得注意的是，在所有模型中，与二噁英相关的心脏致畸性都与心血管细胞凋亡增加和心肌细胞增殖减少有关。虽然鱼类和鸟类物种中的心脏致畸性与明显的发病率和死亡率相关，但鼠胚并非如此。然而，在发育过程中暴露于二噁英的鼠类后代表现出心脏肥大，并且成年后对第二次心血管损伤的敏感性增加。因此，尽管哺乳动物胚胎对二噁英和二噁英类化合物引起的心血管缺陷不太敏感，但发育暴露会增加日后患心血管疾病的风险。发育暴露于二噁英类化学物质对人类心血管疾病易感性的影响尚不清楚。然而，最近的动物研究证实了人类流行病学研究的结果，即成年期接触二噁英与高血压和心血管疾病有关。
