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 (AgNO₃, 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.

中文翻译：

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斑马鱼胚胎的减少转录组分析优先考虑具有不良心血管活动的环境化合物

心血管疾病是人类过早死亡的主要原因，并且仍然是全球公共卫生挑战。虽然年龄、性别、家族史和错误的营养有所贡献，但我们对作为心血管干扰物的化合物的理解还远未完成。在这里，我们的目标是通过减少转录组图谱 (RTA) 方法识别心血管干扰物，该方法整合了斑马鱼的大规模转录组数据集，并编译了与心血管疾病相关的特定基因组。在涵盖 81 种环境化合物的 767 种基因表达谱中，确定了 11 种优先化合物在转录水平上对心血管系统的影响最大。其中，金属（AgNO ₃、银纳米粒子、砷）和杀虫剂/杀菌剂（利谷隆、对羟基苯甲酸甲酯、三氯生和三甲基氯锡）被认为具有最显着的效果。通过百分比值进一步识别不同的转录特征，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，实验证实了优先化合物的心血管失调。实验验证准确率高达62.9%。http://www.envh.sjtu.edu.cn/cardionet.jsp 进一步提供了基于网络的 RTA 分析工具 Cardionet，用于快速发现心血管干扰物。