Abstract

The proposed studies are designed to test the hypothesis that A1 adenosine receptors (A1ARs) activate functional effector systems in embryonic hearts to regulate cardiac activity. Further, it is proposed that A1AR activation during critical periods of heart formation affects cardiac structural development.
Four specific aims are proposed. 1) The effector systems through which A1ARs influence fetal cardiac physiology will be defined. 2) A determination will be made whether A1AR activation influences cardiac structural development. 3) Transgenic mice will be generated by fusing the wild-type A1AR receptor with the atrial natriuretic factor promoter. 4) The A1AR promoter will be characterized and transgenic animals expressing high affinity A1ARs will be generated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058442-04
Application #
6184368
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Wang, Lan-Hsiang
Project Start
1997-08-15
Project End
2001-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
4
Fiscal Year
2000
Total Cost
$270,552
Indirect Cost

  Institution

Name
Yale University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Rivkees, Scott A; Wendler, Christopher C (2017) Long-term consequences of disrupting adenosine signaling during embryonic development. Mol Aspects Med 55:110-117
Wendler, Christopher C; Busovsky-McNeal, Melissa; Ghatpande, Satish et al. (2009) Embryonic caffeine exposure induces adverse effects in adulthood. FASEB J 23:1272-8
Ghatpande, Satish K; Billington Jr, Charles J; Rivkees, Scott A et al. (2008) Hypoxia induces cardiac malformations via A1 adenosine receptor activation in chicken embryos. Birth Defects Res A Clin Mol Teratol 82:121-30
Wendler, Christopher C; Amatya, Salina; McClaskey, Carolyn et al. (2007) A1 adenosine receptors play an essential role in protecting the embryo against hypoxia. Proc Natl Acad Sci U S A 104:9697-702
Wendler, Christopher C; Rivkees, Scott A (2006) Sphingosine-1-phosphate inhibits cell migration and endothelial to mesenchymal cell transformation during cardiac development. Dev Biol 291:264-77
Zhao, Zhiyong; Rivkees, Scott A (2004) Rho-associated kinases play a role in endocardial cell differentiation and migration. Dev Biol 275:183-91
Gascard, Philippe; Parra, Marilyn K; Zhao, Zhiyong et al. (2004) Putative tumor suppressor protein 4.1B is differentially expressed in kidney and brain via alternative promoters and 5' alternative splicing. Biochim Biophys Acta 1680:71-82
Porter Jr, George A; Makuck, Ryan F; Rivkees, Scott A (2003) Intracellular calcium plays an essential role in cardiac development. Dev Dyn 227:280-90
Zhao, Zhiyong; Rivkees, Scott A (2003) Rho-associated kinases play an essential role in cardiac morphogenesis and cardiomyocyte proliferation. Dev Dyn 226:24-32
Porter Jr, George A; Makuck, Ryan F; Rivkees, Scott A (2002) Reduction in intracellular calcium levels inhibits myoblast differentiation. J Biol Chem 277:28942-7

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