title: Exposure to low-dose trichloroethylene alters shear stress gene expression and function in the developing chick heart.
abstract: Trichloroethylene is an organic solvent used as an industrial degreasing agent. Due to its widespread use and volatile nature, TCE is a common environmental contaminant. Trichloroethylene exposure has been implicated in the etiology of heart defects in human populations and animal models. Recent data suggest misregulation of Ca2+ homeostasis in H9c2 cardiomyocyte cell line after TCE exposure. We hypothesized that misregulation of Ca2+ homeostasis alters myocyte function and leads to changes in embryonic blood flow. In turn, changes in cardiac flow are known to cause cardiac malformations. To investigate this hypothesis, we dosed developing chick embryos in ovo with environmentally relevant doses of TCE (8 and 800 ppb). RNA was isolated from control and treated embryos at specific times in development for real-time PCR analysis of blood flow markers. Effects were observed on Endothelin-1 (ET-1), Nitric Oxide Synthase-3 (NOS-3) and Krüppel-like Factor 2 (KLF2) expression relative to TCE exposure and consistent with reduced flow. Further, we measured function in the developing heart after TCE exposure by isolating cardiomyocytes and measuring half-width of contraction and sarcomere lengths. These functional data showed a significant increase in half-width of contraction after TCE exposure. These data suggest that perturbation of cardiac function contributes to the etiology of congenital heart defects in TCE-exposed embryos.
authors.affiliation: Department of Cell Biology and Anatomy, University of Arizona, 1501 N Campbell Avenue, PO Box 245044, Tucson, AZ 85724-5044, USA.
authors.forename: Om
authors.initials: O
authors.lastname: Makwana
authors.forename: Nicholas M P
authors.initials: NM
authors.lastname: King
authors.forename: Lauren
authors.initials: L
authors.lastname: Ahles
authors.forename: Ornella
authors.initials: O
authors.lastname: Selmin
authors.forename: Henk L
authors.initials: HL
authors.lastname: Granzier
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Runyan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001783:Blood Flow Velocity; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D012997:Solvents / Q000633:toxicity*; D013314:Stress, Mechanical; D013723:Teratogens / Q000633:toxicity*; D014241:Trichloroethylene / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D051741:Kruppel-Like Transcription Factors; D012997:Solvents; D013723:Teratogens; D014241:Trichloroethylene; D052250:Nitric Oxide Synthase Type III