{"doi":"10.1093/toxsci/kfab125","title":"Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction","abstract":"Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals, and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. Recent population-based studies indicate that benzene exposure is associated with an increased risk for heart failure. Nonetheless, it is unclear whether benzene exposure is sufficient to induce and/or exacerbate heart failure. We examined the effects of benzene (50 ppm, 6 h/day, 5 days/week, and 6 weeks) or high-efficiency particulate absorbing-filtered air exposure on transverse aortic constriction (TAC)-induced pressure overload in male C57BL/6J mice. Our data show that benzene exposure had no effect on cardiac function in the Sham group; however, it significantly compromised cardiac function as depicted by a significant decrease in fractional shortening and ejection fraction, as compared with TAC/Air-exposed mice. RNA-seq analysis of the cardiac tissue from the TAC/benzene-exposed mice showed a significant increase in several genes associated with adhesion molecules, cell-cell adhesion, inflammation, and stress response. In particular, neutrophils were implicated in our unbiased analyses. Indeed, immunofluorescence studies showed that TAC/benzene exposure promotes infiltration of CD11b+/S100A8+/myeloperoxidase+-positive neutrophils in the hearts by 3-fold. In vitro, the benzene metabolites, hydroquinone, and catechol, induced the expression of P-selectin in cardiac microvascular endothelial cells by 5-fold and increased the adhesion of neutrophils to these endothelial cells by 1.5- to 2.0-fold. Benzene metabolite-induced adhesion of neutrophils to the endothelial cells was attenuated by anti-P-selectin antibody. Together, these data suggest that benzene exacerbates heart failure by promoting endothelial activation and neutrophil recruitment.","journal":"Toxicological Sciences","year":2021,"id":172943,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":360817,"name":"Sujith Dassanayaka","orcid":"0000-0002-8627-6731","position":1,"is_corresponding":false},{"id":355674,"name":"Marina V. Malovichko","orcid":"0000-0003-2127-5858","position":2,"is_corresponding":false},{"id":709882,"name":"Caitlin M. Howard","orcid":"0000-0002-9311-6664","position":3,"is_corresponding":false},{"id":710674,"name":"Lauren F. Garrett","orcid":null,"position":4,"is_corresponding":false},{"id":420794,"name":"Shizuka Uchida","orcid":"0000-0003-4787-8067","position":5,"is_corresponding":false},{"id":362593,"name":"Kenneth R. Brittian","orcid":null,"position":6,"is_corresponding":false},{"id":293993,"name":"Daniel J. Conklin","orcid":"0000-0002-8385-9982","position":7,"is_corresponding":false},{"id":360821,"name":"Steven P. Jones","orcid":"0000-0001-5376-8089","position":8,"is_corresponding":false},{"id":355676,"name":"Sanjay Srivastava","orcid":"0000-0002-8989-0438","position":9,"is_corresponding":false},{"id":709881,"name":"Igor N. Zelko","orcid":"0000-0003-3976-3884","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-18T23:46:45.768135Z","pmid":"34718823","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}