227: Blockade of CD4+ T cells prior to placental insult, attenuates hypertension in response to placental ischemia

Abstract

attenuates hypertension in response to placental ischemia Sarah Novotny, Kedra Wallace, Pushpinder Dhillon, Janae Moseley, Judith Heath, James N Martin Jr, Babbette LaMarca University of Mississippi Medical Center, Obstetrics and Gynecology, Jackson, MS OBJECTIVE: Preeclampsia is associated with hypertension, proteinuria, chronic immune activation involving activated CD4 T cells, inflammatory cytokines, and agonistic autoantibodies. Research from our laboratory has shown that hypertension in the chronic placental ischemia rat model of preeclampsia (RUPP) is associated with CD4 T cell activation, inflammatory cytokines, autoantibodies and renal dysfunction. Our most recent studies indicate that adoptive transfer of RUPP CD4 T cells into normal pregnant rats causes hypertension and much of the pathophysiology seen in women with preeclampsia. Therefore, we hypothesize that CD4 T cell activation blockade with abatacept (Orencia) would attenuate hypertension in RUPP pregnant rats. STUDY DESIGN: To answer this question four groups of pregnant rats were examined: normal pregnant (NP, n 20), Reduced uterine perfusion pressure (RUPP, n 20), NP orencia (NP O; n 12) and RUPP orencia (RUPP O; n 19). Orencia, abatacept, (250mg/kg) was infused i.v. via jugular catheter over a 20 minute period on day 13 to NP (n 31)rats, 19 of which underwent the RUPP surgical procedure on day 14, same day as RUPP controls. On day 18 indwelling carotid catheters were inserted into all groups and on day 19 MAP was analyzed, plasma collected for FACS analysis of CD4 T cells, and serum was collected for ELISA. RESULTS: MAP increased from 94 / 2 mmHg in NP rats to 123 / 3 mmHg in RUPP rats. This response was attenuated with CD4 T cell blockade, MAP was 104 / 2 mmHg in RUPP O, and had no effect in the NP O (96 / 2 mmHg). Circulating CD4 T cells increased in RUPPs compared to NP rats, 66% / 3% and 55.5% / 2.7% respectively (p 0.04) but was attenuated in RUPP O rats (54.8 / 2.5%) and was 59 / 4% in NP O. The twofold increase in TNF alpha seen in RUPPs (277 / 47 pg/ml) was decreased to 80 / 18 pg/ml in RUPPs O. CONCLUSION: Blockade of CD4 T cells prior to the initial placental insult attenuated hypertension in RUPP rats, indicating the importance of immune activation in the pathophysiology of hypertension in response to placental ischemia. 228 Biochemical markers of bone turnover and bone mineral density during pregnancy in twin pregnancy and singleton pregnancy SiWon Lee, Jae Hyug Yang, Kwang Moon Yang, Jung Yeol Han, June Seek Choi, Hyun Kyeong Ahn, Min Hyuong Kim, Hyun Mee Ryu, Moon Young Kim, Jin Hoon Chung, Yoo Jung Han Cheil General Hospital and Women’s Healthcare Center, Obstetrics and Gynecology, Seoul, CT, South Korea, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine, Obstetrics and Gynecology, Seoul, CT, Korea, Cheil General Hospital, Obstetrics and Gynecology, Seoul, CT, Korea OBJECTIVE: To examine the influence of twin pregnancy on biochemical markers of bone turnover and bone mineral density (BMD) during pregnancy by comparing with singleton pregnancy. STUDY DESIGN: Between February 2004 and February 2008, we conducted a prospective study to show the patterns of changes in biochemical markers of bone turnover and bone mineral density (BMD) during pregnancy in twin and singleton pregnancies. Forty-eight twin and 41 singleton pregnant women were included. In both cross-sectional and longitudinal studies, ultrasound BMD and serum markers of bone resorption ( -Crosslaps) and bone formation (total alkaline phosphatase (ALP), osteocalcin (OC)), total calcium, phosphorus and parathyroid hormone were measured during each trimester of pregnancy. RESULTS: BMD was generally lower in twin pregnancy than in singleton pregnancy. BMD decreased until second trimester in both groups. However, in the third trimester, BMD started to recover in singleton pregnancy whereas it continued to decrease in twin pregnancy although not statistically significant (p 0.308). In twin pregnancy, marker of bone resorption ( -Crosslaps) was lower in the first trimester and higher in the third trimester compared to singleton pregnancy. Markers of bone formation (ALP, OC) also showed higher levels in the third trimester in twin pregnancy. In cross-sectional study, serum calcium and phosphorus were significantly higher and serum PTH was significantly lower in twin pregnancy than in singleton pregnancy (p 0.001). CONCLUSION: In twin pregnancy, BMD was lower and biochemical markers of bone turnover showed generally earlier and larger increases during pregnancy signifying higher fetal demand for calcium compared to the singleton pregnancy. Therefore, higher levels of calcium and vitamin D supplementation should be recommended for women with twin pregnancy.