Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction.
Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction.
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慢性苯暴露会加重压力过载引起的心脏功能障碍。
DOI：
10.1093/toxsci/kfab125
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Srivastava,Sanjay
中科院分区：
文献类型：
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作者：
Zelko,IgorN;Dassanayaka,Sujith;Malovichko,MarinaV;Howard,CaitlinM;Garrett,LaurenF;Uchida,Shizuka;Brittian,KennethR;Conklin,DanielJ;Jones,StevenP;Srivastava,Sanjay
苯是一种普遍存在的环境污染物，广泛存在于家用产品、石化产品和香烟烟雾中。苯是众所周知的人类和实验动物致癌物；然而，人们对苯的心血管毒性知之甚少。最近的基于人群的研究表明，接触苯与心力衰竭风险增加有关。尽管如此，尚不清楚苯暴露是否足以诱发和/或加剧心力衰竭。我们研究了苯（50ppm、6小时/天、5天/周和6周）或高效颗粒吸收过滤空气暴露对雄性C57BL/6J小鼠横主动脉缩窄（TAC）引起的压力超负荷的影响。我们的数据表明，苯暴露对假手术组的心脏功能没有影响；然而，与暴露于TAC/空气的小鼠相比，它显着损害了心脏功能，表现为缩短分数和射血分数显着降低。对暴露于 TAC/苯的小鼠心脏组织的 RNA 序列分析显示，与粘附分子、细胞间粘附、炎症和应激反应相关的多个基因显着增加。特别是，中性粒细胞参与了我们的公正分析。事实上，免疫荧光研究表明，TAC/苯暴露可促进心脏中 CD11b+/S100A8+/髓过氧化物酶+阳性中性粒细胞的浸润增加 3 倍。在体外，苯代谢物、对苯二酚和儿茶酚可诱导心脏微血管内皮细胞中 P-选择素的表达增加 5 倍，并使中性粒细胞与这些内皮细胞的粘附增加 1.5- 至 1.5 倍。 2.0倍。抗 P-选择素抗体可减弱苯代谢物诱导的中性粒细胞与内皮细胞的粘附。总之，这些数据表明苯通过促进内皮激活和中性粒细胞募集而加剧心力衰竭。
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.