Cardiac Surgery, Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1733-40. doi: 10.1161/ATVBAHA.110.211011. Epub 2010 Jul 1.
To validate the hypothesis that the toxic heavy metal lead (Pb) may be linked to cardiovascular diseases via the initiation of atherosclerosis, in vivo and in vitro studies were conducted.
During the human study part of this project, serum Pb levels of healthy young women were correlated to carotid intima-media thickness. Multivariate logistic regression analyses showed that increased serum Pb levels were significantly associated with an increased intima-media thickness (P=0.01; odds ratio per SD unit, 1.6 [95% CI, 1.1 to 2.4]). In vitro, Pb induced an increase in interleukin 8 production and secretion by vascular endothelial cells. Nuclear factor erythroid 2-related factor-2 is the crucial transcription factor involved in Pb-induced upregulation of interleukin 8. Endothelial cell-secreted interleukin 8 triggered intimal invasion of smooth muscle cells and enhanced intimal thickening in an arterial organ culture model. This phenomenon was further enhanced by Pb-increased elastin synthesis of smooth muscle cells.
Our data support the hypothesis that Pb is a novel, independent, and significant risk factor for intimal hyperplasia.
通过体内和体外研究，验证假设，即有毒重金属铅（Pb）可能通过动脉粥样硬化的发生与心血管疾病有关。
在该项目的人体研究部分中，将健康年轻女性的血清 Pb 水平与颈动脉内膜中层厚度相关联。多变量逻辑回归分析表明，血清 Pb 水平升高与内膜中层厚度增加显著相关（P=0.01；每标准差单位的优势比，1.6 [95%置信区间，1.1 至 2.4]）。在体外，Pb 诱导血管内皮细胞中白细胞介素 8 的产生和分泌增加。核因子红细胞 2 相关因子 2 是 Pb 诱导白细胞介素 8 上调所涉及的关键转录因子。内皮细胞分泌的白细胞介素 8 触发平滑肌细胞内膜浸润，并在动脉器官培养模型中增强内膜增厚。Pb 增加平滑肌细胞的弹性蛋白合成进一步增强了这种现象。
我们的数据支持 Pb 是内膜增生的一种新型、独立且重要的危险因素的假设。
