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 language | English (US) |
|---|---|
| Pages (from-to) | 100-107 |
| Number of pages | 8 |
| Journal | Cardiovascular Toxicology |
| Volume | 10 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jun 2010 |
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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 journal › Article
}
TY - JOUR
T1 - Exposure to low-dose trichloroethylene alters shear stress gene expression and function in the developing chick heart
AU - Makwana, Om
AU - King, Nicholas M P
AU - Ahles, Lauren
AU - Selmin, Ornella
AU - Granzier, Hendrikus "Henk"
AU - Runyan, Raymond B
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - Embryonic heart
KW - KLF2
KW - NOS-3
KW - TCE
KW - Teratology
UR - http://www.scopus.com/inward/record.url?scp=77956394773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956394773&partnerID=8YFLogxK
U2 - 10.1007/s12012-010-9066-y
DO - 10.1007/s12012-010-9066-y
M3 - Article
C2 - 20186580
AN - SCOPUS:77956394773
VL - 10
SP - 100
EP - 107
JO - Cardiovascular Toxicology
JF - Cardiovascular Toxicology
SN - 1530-7905
IS - 2
ER -