T T Kanninen1, A Jayaram, S Jaffe Lifshitz, S S Witkin. 1. Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
Abstract
OBJECTIVE: Mechanisms leading to pre-eclampsia remain incompletely defined. Autophagy is a conserved process necessary for cell survival under adverse conditions. We hypothesised that sera from women with healthy pregnancies and women with pre-eclampsia differed in autophagy induction. DESIGN: A case-control study. SETTING: Weill Cornell Medical College. POPULATION: Twenty-four normotensive pregnant women and 20 women with pre-eclampsia. METHODS: Sera were incubated with peripheral blood mononuclear cells (PBMCs) from female donors. After 48 hours the PBMCs were lysed and the intracellular concentration of p62 was determined by enzyme-linked immunosorbent assay (ELISA). Its concentration is inversely proportional to the extent of autophagy induction. Serum endoglin, interleukin 13 (IL-13), insulin-like growth factor 1 (IGF-1), and transforming growth factor β1 (TGF-β1) levels were quantitated by ELISA. MAIN OUTCOME MEASURES: Differences in autophagy induction and serum mediator levels in the two groups. RESULTS: Autophagy induction increased with gestational age in sera from normotensive women (P = 0.0045), but not in women with pre-eclampsia. In the presence of an autophagy inducer, the capacity for autophagy induction decreased with gestational age in sera from women with pre-eclampsia (P = 0.0235), but not from controls. Endoglin concentrations were positively associated with the extent of autophagy induction in controls only (P = 0.0141). There was no association between autophagy and serum IL-13, IGF-1, or TGF-β1 levels. CONCLUSIONS: Sera from women with pre-eclampsia differ from normotensive women by their inability to induce autophagy as a function of gestational age.
OBJECTIVE: Mechanisms leading to pre-eclampsia remain incompletely defined. Autophagy is a conserved process necessary for cell survival under adverse conditions. We hypothesised that sera from women with healthy pregnancies and women with pre-eclampsia differed in autophagy induction. DESIGN: A case-control study. SETTING: Weill Cornell Medical College. POPULATION: Twenty-four normotensive pregnant women and 20 women with pre-eclampsia. METHODS: Sera were incubated with peripheral blood mononuclear cells (PBMCs) from female donors. After 48 hours the PBMCs were lysed and the intracellular concentration of p62 was determined by enzyme-linked immunosorbent assay (ELISA). Its concentration is inversely proportional to the extent of autophagy induction. Serum endoglin, interleukin 13 (IL-13), insulin-like growth factor 1 (IGF-1), and transforming growth factor β1 (TGF-β1) levels were quantitated by ELISA. MAIN OUTCOME MEASURES: Differences in autophagy induction and serum mediator levels in the two groups. RESULTS: Autophagy induction increased with gestational age in sera from normotensive women (P = 0.0045), but not in women with pre-eclampsia. In the presence of an autophagy inducer, the capacity for autophagy induction decreased with gestational age in sera from women with pre-eclampsia (P = 0.0235), but not from controls. Endoglin concentrations were positively associated with the extent of autophagy induction in controls only (P = 0.0141). There was no association between autophagy and serum IL-13, IGF-1, or TGF-β1 levels. CONCLUSIONS: Sera from women with pre-eclampsia differ from normotensive women by their inability to induce autophagy as a function of gestational age.
Authors: Jamie F Merves; Kelly A Whelan; Alain J Benitez; Amanda B Muir; Glenn T Furuta; Mei-Lun Wang; Gary W Falk; Jonathan M Spergel; Hiroshi Nakagawa Journal: Am J Gastroenterol Date: 2016-01 Impact factor: 10.864
Authors: Dimitrios Nasioudis; Larry J Forney; G Maria Schneider; Karol Gliniewicz; Michael France; Allison Boester; Mio Sawai; Jessica Scholl; Steven S Witkin Journal: Sci Rep Date: 2017-08-31 Impact factor: 4.379