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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\u2009ppm, 6\u2009h\/day, 5\u2009days\/week, and 6\u2009weeks) 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.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab125","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T23:14:36Z","timestamp":1634858076000},"page":"64-76","source":"Crossref","is-referenced-by-count":28,"title":["Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction"],"prefix":"10.1093","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-3884","authenticated-orcid":false,"given":"Igor N","family":"Zelko","sequence":"first","affiliation":[{"name":"Superfund Research Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Envirome Institute, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujith","family":"Dassanayaka","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina V","family":"Malovichko","sequence":"additional","affiliation":[{"name":"Superfund Research Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Envirome Institute, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin M","family":"Howard","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Envirome Institute, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren F","family":"Garrett","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Envirome Institute, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-8067","authenticated-orcid":false,"given":"Shizuka","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Center for RNA Medicine, Aalborg University, Copenhagen, SV, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth R","family":"Brittian","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Envirome Institute, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Conklin","sequence":"additional","affiliation":[{"name":"Superfund Research Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Envirome Institute, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P","family":"Jones","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Envirome Institute, University of Louisville, Louisville, Kentucky 40202, USA"},{"name":"Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Superfund Research Center, University of Louisville, Louisville, Kentucky 40202, 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