This candidate is an Associate Professor of Obstetrics and Gynecology (OB/GYN) at Virginia Commonwealth University. He has played a key role in Department of OB/GYN in the research program in preeclampsia. His career goals are: 1) to be a leading scientist in patient- oriented research in preeclampsia, and 2) to train junior clinicians as bio- medical scientists. This application has been written to consolidate his status as a clinical scientist and teacher. During the period of the proposed studies, the candidate will perform research and serve as a mentor to junior faculty, residents, and colleagues. The proposed studies involve a new, multidisciplinary approach to understanding the role of lipid peroxides in the development of hypertension in preeclampsia. Preeclampsia is a health problem of pregnancy that affects approximately 5-8 percent of women and is associated with significant maternal/neonatal morbidity and mortality. It is characterized by hypertension thought to be secondary to vascular endothelial activation and dysfunction. The mechanisms that cause hypertension in preeclampsia are poorly understood but are thought to be mediated by decreased vascular endothelial nitric oxide (NO) production. Studies in our laboratory have shown that lipid peroxides in preeclamptic plasma activates endothelial cells and may reduce eNOS derived NO availability. We hypothesize that increased lipid peroxides in preeclampsia decrease endothelial eNOS generated bioavailable NO resulting in decreased flow-mediated endothelial-dependent vascular relaxation. To test this hypothesis, the following specific aims will be performed:
Aim 1) Do patients with preeclampsia have decreased flow- mediated endothelial-dependent vascular relaxation? Aim 2) Do lipid peroxides in preeclamptic plasma decrease endothelial cell eNOS generated bioavailable NO? Aim 3) Is flow-mediated endothelial-dependent vascular relaxation decreased during early pregnancy in women who subsequently develop preeclampsia? Aims 4) Will antioxidant therapy improve flow-mediated endothelialdependent vascular relaxation in patient at risk for preeclampsia? The institutional and departmental environment as well as the facilities and resources are excellent for career development in academic medicine. The K24 award will protect this candidates time and help him to mature into a senior investigator in OB/GYN.
| Ryu, Seongho; Huppmann, Alison R; Sambangi, Nirmala et al. (2007) Increased leukocyte adhesion to vascular endothelium in preeclampsia is inhibited by antioxidants. Am J Obstet Gynecol 196:400.e1-7;discussion 400.e7-8 |
| Takacs, Peter; Green, Kermic L; Nikaeo, Athip et al. (2003) Increased vascular endothelial cell production of interleukin-6 in severe preeclampsia. Am J Obstet Gynecol 188:740-4 |
| Kauma, Scott; Takacs, Peter; Scordalakes, Constantine et al. (2002) Increased endothelial monocyte chemoattractant protein-1 and interleukin-8 in preeclampsia. Obstet Gynecol 100:706-14 |
