Increased Expression of Hypoxia-Inducible Factor-1 Alpha in the Late Third Trimester Human Placenta from Patients with Chronic Hypertension
Hao Wu, Yanelba Toribio, Sandra Cerda, Carmen Sarita-Reyes. Boston Medical Center, Boston, MA
Background: Hypoxia-inducible factor 1(HIF-1) is a critical transcription factor involved in oxygen homeostasis that regulates adaptive responses to hypoxia, including angiogenesis. In a normal pregnancy, there is extensive angiogenesis and vascularization of placenta. The expression of alpha submit of HIF-1 (HIF-1α) is increased under physiological hypoxia in early placentas and it is abnormally elevated in pre-eclamptic placental tissue. Since both diabetes and hypertension are known risk factors for preeclampsia, we studied the protein expression of HIF-1α in these conditions and evaluate its use as a marker of fetal hypoxia.
Design: Immunohistochemistry studies for HIF-1α stains were performed on late third trimester (≥ 35 weeks) placenta parenchyma. Consecutive cases of patients with hypertension and diabetes delivered at our institution from January to August 2010 were included, 10 age/race/parity comparable cases without significant medical history were selected as negative controls. Only nuclear staining of HIF-1α was considered positive, and Fisher's exact test was used to compare the percentage of positive cases between groups.
Results: 69 cases were included in our study, including 14 cases of diabetes, 45 cases of hypertension and 10 control cases. 20 patients presented with preeclampsia at the time of delivery. Nuclear expression of HIF-1α was seen in 34 cases (49%) of all 69 placentas, including 6 cases of diabetes (43%), 24 cases of hypertension (53%) and 4 cases of control patients (40%). 8 out of 20 cases with preeclampsia showed positive HIF-1α staining (40%). Upon further stratifying the hypertension patients into chronic hypertension group (15 cases) and pregnancy-induced hypertension group (30 cases), 11 cases of chronic hypertension placentas (73%) showed HIF-1α staining, while only 13 cases of pregnancy-induced hypertension placentas (43%) was positive; however, neither hypertension group had statistically higher HIF-1α staining than the control group (p>0.05). We did not observe any correlation between HIF-1α expression and microscopic vasculopathy.
Conclusions: There was increased HIF-1α protein expression in the placentas from patients with chronic hypertension, while its expression in pregnancy-induced hypertension and diabetes appeared to be comparable to that of placentas without significant medical history. Our data suggest there are different pathophysiological mechanisms between chronic hypertension and pregnancy-induced hypertension that affect late trimester placenta.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 213, Wednesday Afternoon