Cardiovascular disease is the leading cause of death in the United States. However, despite the intense research in this area, current risk factors can only account for 50 percent of diagnosed cases. Exposure to environmental contaminates during cardiovascular development may adversely affect development and increase the risk of cardiovascular disease later in life. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and similar environmental contaminates have been shown to be potent cardiovascular teratogens in all species tested. The action of TCDD is believed to be mediated, at least in part by the aryl hydrocarbon receptor (AhR), which has been shown to induce cell cycle arrest via an interaction with the retinoblastoma (Rb) protein. Preliminary studies in our laboratory have demonstrated that TCDD exposure at d14.5 of gestation in the mouse results in a reduction in cardiomyocyte proliferation at d17.5. This is a potential concern for adult animals as well, since cardiomyocytes are unable to divide after birth, and therefore, a reduction in cardiomyocyte number prior to birth may lead to a life long reduction in total cell number in the heart. Experiments in this study will investigate the mechanism of this effect, and test the hypothesis that TCDD treatment leads to an AhR-dependent reduction in Rb phosphorylation and subsequent reduction in E2F-dependent transcription and G1 cell cycle arrest in embryonic cardiomyocytes. These studies will be conducted using both an in vivo mouse model and a primary cardiomyocyte cell culture system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32ES012855-01
Application #
6742943
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Shreffler, Carol K
Project Start
2003-09-30
Project End
2006-09-29
Budget Start
2003-09-30
Budget End
2004-09-29
Support Year
1
Fiscal Year
2003
Total Cost
$41,608
Indirect Cost
Name
University of New Mexico
Department
Type
Schools of Pharmacy
DUNS #
868853094
City
Albuquerque
State
NM
Country
United States
Zip Code
87131