title: In vitro particulate matter exposure causes direct and lung-mediated indirect effects on cardiomyocyte function.
abstract: 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.
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio;
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Gorr
authors.affiliation: College of Nursing, The Ohio State University, Columbus, Ohio; and.
authors.forename: Dane J
authors.initials: DJ
authors.lastname: Youtz
authors.affiliation: College of Nursing, The Ohio State University, Columbus, Ohio; and.
authors.forename: Clayton M
authors.initials: CM
authors.lastname: Eichenseer
authors.affiliation: College of Nursing, The Ohio State University, Columbus, Ohio; and.
authors.forename: Korbin E
authors.initials: KE
authors.lastname: Smith
authors.affiliation: 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.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Nelin
authors.affiliation: Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Estelle
authors.initials: E
authors.lastname: Cormet-Boyaka
authors.affiliation: 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 Loren.Wold@osumc.edu.
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D052638:Particulate Matter / Q000494:pharmacology*; D051381:Rats; D012518:Sarcomeres / Q000187:drug effects; D001335:Vehicle Emissions
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D018932:Chemokine CCL2; D016207:Cytokines; D052638:Particulate Matter; D001335:Vehicle Emissions; D002118:Calcium
keywords: air pollution; cardiovascular toxicology; in vitro toxicology; particulate matter