The goal of this proposal is to investigate the association between the independent risk factor for atherosclerosis, homocysteine, and the pregnancy-specific vascular syndrome preeclampsia. Preeclampsia is the leading cause of maternal mortality in developed countries, increases perinatal mortality five fold and is associated with an increased risk of cardiovascular disease in later life. These studies will be performed to determine total homocysteine concentrations in normal and preeclamptic pregnancies, and this data will be correlated to known markers of oxidative stress which are postulated to play a role in the pathogenesis of preeclampsia. Furthermore, the nutritional and genetic factors responsible for increased homocysteine will be analyzed to determine the mechanisms leading to hyperhomocysteinemia. Lastly, the effect(s) of hyperhomocystienemia upon the functional modifications of the vasculature in pregnancy will be investigated with the use of a hyperhomocysteinemic transgenic mouse model. This study is designed to determine if the vasculature possess a unique sensitivity to the atherogenic molecule, homocysteine, during pregnancy. These studies may potentially identify a common risk factor for preeclampsia, and more importantly may lead to nutritional modifications to reduce the incidence of preeclampsia, similar to results obtained with nutritional modification in subsets of atherosclerotic patients.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD008310-01
Application #
2412967
Study Section
Special Emphasis Panel (ZRG2-REB (01))
Project Start
1998-01-01
Project End
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Magee-Women's Hospital of Upmc
Department
Type
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Perszyk, Danielle R; Ferguson, Brock; Waxman, Sandra R (2018) Maturation constrains the effect of exposure in linking language and thought: evidence from healthy preterm infants. Dev Sci 21:
Havy, Mélanie; Waxman, Sandra R (2016) Naming influences 9-month-olds' identification of discrete categories along a perceptual continuum. Cognition 156:41-51
Powers, Robert W; Gandley, Robin E; Lykins, David L et al. (2004) Moderate hyperhomocysteinemia decreases endothelial-dependent vasorelaxation in pregnant but not nonpregnant mice. Hypertension 44:327-33
Powers, Robert W; Dunbar, Michael S; Gallaher, Marcia J et al. (2003) The 677 C-T methylenetetrahydrofolate reductase mutation does not predict increased maternal homocysteine during pregnancy. Obstet Gynecol 101:762-6
Powers, Robert W; Majors, Alana K; Cerula, Stacy L et al. (2003) Changes in markers of vascular injury in response to transient hyperhomocysteinemia. Metabolism 52:501-7
Powers, Robert W; Majors, Alana K; Lykins, David L et al. (2002) Plasma homocysteine and malondialdehyde are correlated in an age- and gender-specific manner. Metabolism 51:1433-8
Powers, R W; Evans, R W; Ness, R B et al. (2001) Homocysteine and cellular fibronectin are increased in preeclampsia, not transient hypertension of pregnancy. Hypertens Pregnancy 20:69-77
Powers, R W; Minich, L A; Lykins, D L et al. (1999) Methylenetetrahydrofolate reductase polymorphism, folate, and susceptibility to preeclampsia. J Soc Gynecol Investig 6:74-9
Powers, R W; Evans, R W; Majors, A K et al. (1998) Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation. Am J Obstet Gynecol 179:1605-11