The hypothesis of this application is that focal areas of hypoxic placenta produce inflammatory cytokines (TNF-alpha and beta, IL-1 alpha and beta) which in turn participate in the vascular alterations resulting in preeclampsia during pregnancy. In the first aim, the investigator will determine if normal pregnant and preeclamptic placental villous and decidual explants will express cytokines when subjected to hypoxia.
In aim 2, they will determine if HIF-1 contributes to the hypoxia-inducible cytokine expression by placental tissues.
In aim 3, they will determine if cytokine levels and cytokine mRNA are increased in placental tissues from women with preeclampsia compared to normal pregnant women.
In aim 4, they will search for specific markers of focal areas of placental hypoxia.
In aim 5, they will investigate whether endogenous NO, CO, and/or cGMP regulate the expression of placental cytokines.
| Rajakumar, A; Brandon, H M; Daftary, A et al. (2004) Evidence for the functional activity of hypoxia-inducible transcription factors overexpressed in preeclamptic placentae. Placenta 25:763-9 |
| Rajakumar, A; Doty, K; Daftary, A et al. (2003) Impaired oxygen-dependent reduction of HIF-1alpha and -2alpha proteins in pre-eclamptic placentae. Placenta 24:199-208 |
| Rajakumar, A; Whitelock, K A; Weissfeld, L A et al. (2001) Selective overexpression of the hypoxia-inducible transcription factor, HIF-2alpha, in placentas from women with preeclampsia. Biol Reprod 64:499-506 |
| Rajakumar, A; Conrad, K P (2000) Expression, ontogeny, and regulation of hypoxia-inducible transcription factors in the human placenta. Biol Reprod 63:559-69 |
| Fairchild Benyo, D; Conrad, K P (1999) Expression of the erythropoietin receptor by trophoblast cellsin the human placenta. Biol Reprod 60:861-70 |
