Laboratory of Nutrition and Metabolic Regulation, Institute of Nutrition and Food Technology (INTA), University of Chile, Casilla 138-11, Santiago, Chile.
Toxicol Appl Pharmacol. 2011 Mar 1;251(2):137-45. doi: 10.1016/j.taap.2011.01.001. Epub 2011 Jan 12.
Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-κB expression--a transcription factor sensitive to inflammation and oxidative stress--suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.
一些在成年期观察到的心血管疾病（CVD）与胎儿生长过程中的环境影响有关。在这里，我们表明，母体暴露于镉（一种广泛分布的重金属，也是香烟烟雾的主要成分）能够在成年后代中诱导心血管形态和功能变化。在怀孕时暴露于 30ppm 镉的大鼠的成年后代中评估了心脏形态和血管反应性。超声心动图检查显示心脏形态发生改变，表现为左心室向心性肥厚。此外，我们还观察到成年后代的离体主动脉环中内皮依赖性反应性降低，而内皮非依赖性反应性保持不变。这些效应与成年后代主动脉中血红素加氧酶 1（HO-1）表达增加有关。HO-1 的表达在雌性中高于雄性，这一发现可能与血管细胞粘附分子 1（VCAM-1）的性别依赖性表达有关，成年雌性中的 VCAM-1 水平较低。所有这些长期后果都伴随着正常的出生体重和后代胎儿和成年组织中未检测到镉的存在而出现。然而，在胎盘组织中检测到了镉的水平，并与 NF-κB 表达的增加相关，NF-κB 是一种对炎症和氧化应激敏感的转录因子，这表明胎盘机制会影响与心血管系统发育相关的基因。我们的研究结果首次提供了直接的实验证据，支持了怀孕期间暴露于镉会重新编程后代心血管发育，这反过来可能会导致 CVD 的长期风险增加。
