Gorr Matthew W, Youtz Dane J, Eichenseer Clayton M, Smith Korbin E, Nelin Timothy D, Cormet-Boyaka Estelle, Wold Loren E
Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio;
College of Nursing, The Ohio State University, Columbus, Ohio; and.
Am J Physiol Heart Circ Physiol. 2015 Jul 1;309(1):H53-62. doi: 10.1152/ajpheart.00162.2015. Epub 2015 May 8.
Particulate matter (PM) exposure induces a pathological response from both the lungs and the cardiovascular system. PM is capable of both manifestation into the lung epithelium and entrance into the bloodstream. Therefore, PM has the capacity for both direct and lung-mediated indirect effects on the heart. In the present studies, we exposed isolated rat cardiomyocytes to ultrafine particulate matter (diesel exhaust particles, DEP) and examined their contractile function and calcium handling ability. In another set of experiments, lung epithelial cells (16HBE14o- or Calu-3) were cultured on permeable supports that allowed access to both the basal (serosal) and apical (mucosal) media; the basal media was used to culture cardiomyocytes to model the indirect, lung-mediated effects of PM on the heart. Both the direct and indirect treatments caused a reduction in contractility as evidenced by reduced percent sarcomere shortening and reduced calcium handling ability measured in field-stimulated cardiomyocytes. Treatment of cardiomyocytes with various anti-oxidants before culture with DEP was able to partially prevent the contractile dysfunction. The basal media from lung epithelial cells treated with PM contained several inflammatory cytokines, and we found that monocyte chemotactic protein-1 was a key trigger for cardiomyocyte dysfunction. These results indicate the presence of both direct and indirect effects of PM on cardiomyocyte function in vitro. Future work will focus on elucidating the mechanisms involved in these separate pathways using in vivo models of air pollution exposure.
接触颗粒物（PM）会引发肺部和心血管系统的病理反应。PM既能在肺上皮细胞中表现出来，又能进入血液循环。因此，PM对心脏具有直接和通过肺部介导的间接影响。在本研究中，我们将分离的大鼠心肌细胞暴露于超细颗粒物（柴油废气颗粒，DEP）中，并检测其收缩功能和钙处理能力。在另一组实验中，将肺上皮细胞（16HBE14o-或Calu-3）培养在可渗透的支持物上，该支持物允许同时接触基底（浆膜）和顶端（黏膜）培养基；使用基底培养基培养心肌细胞，以模拟PM对心脏的间接、通过肺部介导的影响。直接和间接处理均导致收缩性降低，这在电场刺激的心肌细胞中表现为肌节缩短百分比降低和钙处理能力降低。在用DEP培养之前用各种抗氧化剂处理心肌细胞能够部分预防收缩功能障碍。用PM处理的肺上皮细胞的基底培养基中含有几种炎性细胞因子，并且我们发现单核细胞趋化蛋白-1是心肌细胞功能障碍的关键触发因素。这些结果表明PM在体外对心肌细胞功能存在直接和间接影响。未来的工作将集中于使用空气污染暴露的体内模型阐明这些不同途径所涉及的机制。
