Exposure to low-dose trichloroethylene alters shear stress gene expression and function in the developing chick heart

Om Makwana, Nicholas M P King, Lauren Ahles, Ornella Selmin, Hendrikus "Henk" Granzier, Raymond B Runyan

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)100-107
Number of pages8
JournalCardiovascular Toxicology
Volume10
Issue number2
DOIs
StatePublished - Jun 2010

Fingerprint

Trichloroethylene
Cardiac Myocytes
Gene expression
Shear stress
Homeostasis
Embryonic Structures
Gene Expression
Sarcomeres
Congenital Heart Defects
Endothelin-1
Blood
Chick Embryo
Nitric Oxide Synthase
Muscle Cells
Real-Time Polymerase Chain Reaction
Defects
Animal Models
RNA
Cell Line
Organic solvents

Keywords

  • Embryonic heart
  • KLF2
  • NOS-3
  • TCE
  • Teratology

ASJC Scopus subject areas

  • Toxicology
  • Cardiology and Cardiovascular Medicine
  • Molecular Biology
  • Medicine(all)

Cite this

Exposure to low-dose trichloroethylene alters shear stress gene expression and function in the developing chick heart. / Makwana, Om; King, Nicholas M P; Ahles, Lauren; Selmin, Ornella; Granzier, Hendrikus "Henk"; Runyan, Raymond B.

In: Cardiovascular Toxicology, Vol. 10, No. 2, 06.2010, p. 100-107.

Research output: Contribution to journalArticle

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