Journal
ENVIRONMENTAL SCIENCE & TECHNOLOGY
Volume 57, Issue 12, Pages 4959-4970Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.est.2c08920
Keywords
reduced transcriptome analysis; prioritization; cardiovascular disruption; metal; biocides; pesticides; zebrafish; cardiovascular toxicity
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Cardiovascular diseases are a major cause of premature death and a global public health challenge. Using a reduced transcriptome atlas approach, researchers have identified 11 priority compounds with significant effects on the cardiovascular system at the transcriptional level. These compounds, including metals and pesticides/biocides, were experimentally confirmed to dysregulate cardiovascular physiology and lipid profiles in zebrafish.
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.
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