PT  - JOURNAL ARTICLE
AU  - Igor N. Zelko
AU  - Sujith Dassanayaka
AU  - Marina V. Malovichko
AU  - Caitlin M. Howard
AU  - Lauren F. Garrett
AU  - Uchida Shizuka
AU  - Kenneth R. Brittian
AU  - Daniel J. Conklin
AU  - Steven P. Jones
AU  - Sanjay Srivastava
TI  - Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction
AID  - 10.1101/2021.08.31.458367
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.31.458367
4099  - http://biorxiv.org/content/early/2021/09/01/2021.08.31.458367.short
4100  - http://biorxiv.org/content/early/2021/09/01/2021.08.31.458367.full
AB  - 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, 6 weeks) or HEPA-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 1.5-2.0-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.Competing Interest StatementN/A