State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, School of Environmental Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Institute of Biogeochemistry and Pollution Dynamics, Department of Environmental Systems Science, ETH Zürich, CH-8092 Zürich, Switzerland.
Environ Sci Technol. 2023 Mar 28;57(12):4959-4970. doi: 10.1021/acs.est.2c08920. Epub 2023 Mar 19.
Cardiovascular diseases are the leading cause of premature death in humans and remain a global public health challenge. While age, sex, family history, and false nutrition make a contribution, our understanding of compounds acting as cardiovascular disruptors is far from complete. Here, we aim to identify cardiovascular disruptors via a reduced transcriptome atlas (RTA) approach, which integrates large-scale transcriptome data sets of zebrafish and compiles a specific gene panel related to cardiovascular diseases. Among 767 gene expression profiles covering 81 environmental compounds, 11 priority compounds are identified with the greatest effects on the cardiovascular system at the transcriptional level. Among them, metals (AgNO, Ag nanoparticles, arsenic) and pesticides/biocides (linuron, methylparaben, triclosan, and trimethylchlorotin) are identified with the most significant effects. Distinct transcriptional signatures are further identified by the percentage values, indicating that different physiological endpoints exist among prioritized compounds. In addition, cardiovascular dysregulations are experimentally confirmed for the prioritized compounds via alterations of cardiovascular physiology and lipid profiles of zebrafish. The accuracy rate of experimental verification reaches up to 62.9%. The web-based RTA analysis tool, Cardionet, for rapid cardiovascular disruptor discovery was further provided at http://www.envh.sjtu.edu.cn/cardionet.jsp. Our integrative approach yields an efficient platform to discover novel cardiovascular-disrupting chemicals in the environment.
心血管疾病是人类早逝的主要原因，仍是全球公共卫生面临的挑战。虽然年龄、性别、家族史和错误的营养等因素都有一定影响，但我们对作为心血管干扰物的化合物的了解还远远不够。在这里，我们旨在通过一个简化转录组图谱（RTA）方法来识别心血管干扰物，该方法整合了大规模的斑马鱼转录组数据集，并编制了一个与心血管疾病相关的特定基因面板。在涵盖 81 种环境化合物的 767 个基因表达谱中，有 11 种优先化合物在转录水平上对心血管系统有最大影响。其中，金属（AgNO3、银纳米粒子、砷）和农药/生物杀灭剂（利谷隆、对羟基苯甲酸甲酯、三氯生和三甲基氯化锡）的影响最为显著。通过百分比值进一步确定了不同的转录特征，表明优先化合物之间存在不同的生理终点。此外，通过改变斑马鱼的心血管生理学和脂质谱，对优先化合物进行了心血管失调的实验验证。实验验证的准确率高达 62.9%。还提供了一个基于网络的 RTA 分析工具 Cardionet，用于快速发现心血管干扰物，网址为 http://www.envh.sjtu.edu.cn/cardionet.jsp。我们的综合方法提供了一个有效的平台，用于发现环境中的新型心血管干扰化学物质。
