Meera Kumari1, Tracy Kovach2, Brendan Sheehy3, Allyson Zabell4, Rommel Morales5, Sangithan Jules Moodley6, Yogesh G Shah6, Praful V Maroo7, Anjli P Maroo7, W H Wilson Tang8. 1. Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, United States of America. 2. Center for Clinical Genomics, Cleveland Clinic, Cleveland, OH, United States of America. 3. Kettering Medical Center, Kettering, OH, United States of America. 4. Northeast Ohio Medical University, Rootstown, OH, United States of America. 5. Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH, United States of America. 6. Obstetrics and Gynecology, Fairview General Hospital, Fairview Park, OH, United States of America. 7. Department of Cardiovascular Medicine, Fairview General Hospital, Fairview Park, OH, United States of America. 8. Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, United States of America; Center for Clinical Genomics, Cleveland Clinic, Cleveland, OH, United States of America; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America. Electronic address: tangw@ccf.org.
Abstract
BACKGROUND: Corin is a serine protease known to convert B-type natriuretic peptide (BNP) prohormone into BNP and its amino-terminal fragment (NT-proBNP). In mice lacking corin, high blood pressure and proteinuria were found at late gestational stages, with associated delayed trophoblast invasion and impaired spiral artery remodeling in the uterus. We hypothesize that both NT-proBNP and soluble corin elevation predict the presence of preeclampsia in pregnant patients with hypertension. METHODS: We prospectively enrolled 149 pregnant women with a history of chronic hypertension or gestational hypertension presenting at a tertiary-care hospital. We compared plasma NT-proBNP and soluble corin concentrations based on their preeclamptic status. RESULTS: In our study cohort, 62 patients with preeclampsia had lower gestational age than 87 patients without preeclampsia (33.3 ± 3 versus 36.6 ± 3 weeks; P < .001), otherwise the baseline characteristics were similar. We observed higher NT-proBNP concentrations in patients with preeclampsia compared to those without preeclampsia (304.3 [96.34, 570.4] vs. 60.8 [35.61, 136.8] ng/L, P < .001), with no differences between chronic and gestational hypertension. However, the concentration of corin was not statistically different between the two groups (1756 [1214, 2133] vs. 1571 [1171, 1961] ng/L, P = .1087). ROC curve analysis demonstrated stronger predictive value of NT-proBNP compared to soluble corin in predicting the presence of preeclampsia in our study population (AUC 0.7406 vs. 0.5789, P < .0001). CONCLUSION: While corin may contribute to mechanistic underpinnings of the development of preeclampsia in animal models, soluble corin likely has no diagnostic role in human pregnancies for preeclampsia beyond natriuretic peptide levels.
BACKGROUND:Corin is a serine protease known to convert B-type natriuretic peptide (BNP) prohormone into BNP and its amino-terminal fragment (NT-proBNP). In mice lacking corin, high blood pressure and proteinuria were found at late gestational stages, with associated delayed trophoblast invasion and impaired spiral artery remodeling in the uterus. We hypothesize that both NT-proBNP and soluble corin elevation predict the presence of preeclampsia in pregnant patients with hypertension. METHODS: We prospectively enrolled 149 pregnant women with a history of chronic hypertension or gestational hypertension presenting at a tertiary-care hospital. We compared plasma NT-proBNP and soluble corin concentrations based on their preeclamptic status. RESULTS: In our study cohort, 62 patients with preeclampsia had lower gestational age than 87 patients without preeclampsia (33.3 ± 3 versus 36.6 ± 3 weeks; P < .001), otherwise the baseline characteristics were similar. We observed higher NT-proBNP concentrations in patients with preeclampsia compared to those without preeclampsia (304.3 [96.34, 570.4] vs. 60.8 [35.61, 136.8] ng/L, P < .001), with no differences between chronic and gestational hypertension. However, the concentration of corin was not statistically different between the two groups (1756 [1214, 2133] vs. 1571 [1171, 1961] ng/L, P = .1087). ROC curve analysis demonstrated stronger predictive value of NT-proBNP compared to soluble corin in predicting the presence of preeclampsia in our study population (AUC 0.7406 vs. 0.5789, P < .0001). CONCLUSION: While corin may contribute to mechanistic underpinnings of the development of preeclampsia in animal models, soluble corin likely has no diagnostic role in human pregnancies for preeclampsia beyond natriuretic peptide levels.
Authors: Joyce C Y Chan; Ole Knudson; Faye Wu; John Morser; William P Dole; Qingyu Wu Journal: Proc Natl Acad Sci U S A Date: 2005-01-06 Impact factor: 11.205