OBJECTIVE: Preeclampsia is associated with long-term adverse maternal health, such as cardiovascular and metabolic diseases. The objective of this study was to determine whether preeclampsia in a well-characterized animal model that was induced by overexpression of soluble fms-like tyrosine kinase-1 (sFlt1) results in alterations in the maternal circulating proteome that persist long after delivery. STUDY DESIGN: CD-1 mice at day 8 of gestation were injected with adenovirus that carried sFlt1 or the murine immunoglobulin G2α Fc fragment as control. Depleted maternal plasma was analyzed 6 months after delivery by label-free liquid chromatography-mass spectrometry assay. The tandem mass spectrometry data were searched against a mouse database, and the resultant intensity data were used to compare abundance of proteins across disease/control plasma pool. Results were analyzed with ingenuity pathways analysis. Right-tailed Fisher exact test was used to calculate a probability value. RESULTS: Of 150 proteins that are common for both groups, ingenuity pathways analysis determined 105 proteins that were ready for analysis. Diseases and disorders analysis showed significant enrichment of proteins that are associated with cardiovascular disease. Within this cluster, the most abundant proteins were associated with vascular disease, atherosclerosis, and atherosclerotic lesions. Other top disease clusters were inflammatory response, organismal injury and abnormalities, and hematologic and metabolic disease. CONCLUSION: Exposure to sFlt1-induced preeclampsia alters multiple biologic functions in mothers that persist later in life. Our results suggest that some of the long-term adverse outcomes that are associated with preeclampsia actually may be a consequence rather than a mere unmasking of an underlying predisposition. If similar results are found in humans, the development of preventive strategies for preeclampsia should also improve long-term maternal health.
OBJECTIVE:Preeclampsia is associated with long-term adverse maternal health, such as cardiovascular and metabolic diseases. The objective of this study was to determine whether preeclampsia in a well-characterized animal model that was induced by overexpression of soluble fms-like tyrosine kinase-1 (sFlt1) results in alterations in the maternal circulating proteome that persist long after delivery. STUDY DESIGN:CD-1mice at day 8 of gestation were injected with adenovirus that carried sFlt1 or the murine immunoglobulin G2α Fc fragment as control. Depleted maternal plasma was analyzed 6 months after delivery by label-free liquid chromatography-mass spectrometry assay. The tandem mass spectrometry data were searched against a mouse database, and the resultant intensity data were used to compare abundance of proteins across disease/control plasma pool. Results were analyzed with ingenuity pathways analysis. Right-tailed Fisher exact test was used to calculate a probability value. RESULTS: Of 150 proteins that are common for both groups, ingenuity pathways analysis determined 105 proteins that were ready for analysis. Diseases and disorders analysis showed significant enrichment of proteins that are associated with cardiovascular disease. Within this cluster, the most abundant proteins were associated with vascular disease, atherosclerosis, and atherosclerotic lesions. Other top disease clusters were inflammatory response, organismal injury and abnormalities, and hematologic and metabolic disease. CONCLUSION: Exposure to sFlt1-induced preeclampsia alters multiple biologic functions in mothers that persist later in life. Our results suggest that some of the long-term adverse outcomes that are associated with preeclampsia actually may be a consequence rather than a mere unmasking of an underlying predisposition. If similar results are found in humans, the development of preventive strategies for preeclampsia should also improve long-term maternal health.
Authors: Ravi Thadhani; Walter P Mutter; Myles Wolf; Richard J Levine; Robert N Taylor; Vikas P Sukhatme; Jeffrey Ecker; S Ananth Karumanchi Journal: J Clin Endocrinol Metab Date: 2004-02 Impact factor: 5.958
Authors: M T Gervasi; T Chaiworapongsa; P Pacora; N Naccasha; B H Yoon; E Maymon; R Romero Journal: Am J Obstet Gynecol Date: 2001-10 Impact factor: 8.661
Authors: José T Drost; Ganiye Arpaci; Jan Paul Ottervanger; Menko Jan de Boer; Jim van Eyck; Yvonne T van der Schouw; Angela H E M Maas Journal: Eur J Prev Cardiol Date: 2011-08-22 Impact factor: 7.804
Authors: Gareth C McKeeman; Joy E S Ardill; Carolyn M Caldwell; Alyson J Hunter; Neil McClure Journal: Am J Obstet Gynecol Date: 2004-10 Impact factor: 8.661
Authors: Sharon E Maynard; Jiang-Yong Min; Jaime Merchan; Kee-Hak Lim; Jianyi Li; Susanta Mondal; Towia A Libermann; James P Morgan; Frank W Sellke; Isaac E Stillman; Franklin H Epstein; Vikas P Sukhatme; S Ananth Karumanchi Journal: J Clin Invest Date: 2003-03 Impact factor: 14.808
Authors: Richard J Levine; Sharon E Maynard; Cong Qian; Kee-Hak Lim; Lucinda J England; Kai F Yu; Enrique F Schisterman; Ravi Thadhani; Benjamin P Sachs; Franklin H Epstein; Baha M Sibai; Vikas P Sukhatme; S Ananth Karumanchi Journal: N Engl J Med Date: 2004-02-05 Impact factor: 91.245
Authors: Young S Oh; Lawrence J Appel; Zorina S Galis; David A Hafler; Jiang He; Amanda L Hernandez; Bina Joe; S Ananth Karumanchi; Christine Maric-Bilkan; David Mattson; Nehal N Mehta; Gwendolyn Randolph; Michael Ryan; Kathryn Sandberg; Jens Titze; Eser Tolunay; Glenn M Toney; David G Harrison Journal: Hypertension Date: 2016-06-20 Impact factor: 10.190
Authors: Nina D Paauw; Jaap A Joles; Frank T Spradley; Bhavisha Bakrania; Zsuzsanna K Zsengeller; Arie Franx; Marianne C Verhaar; Joey P Granger; A Titia Lely Journal: Am J Physiol Regul Integr Comp Physiol Date: 2017-02-15 Impact factor: 3.619
Authors: Dafina Pruthi; Eliyahu V Khankin; Robert M Blanton; Mark Aronovitz; Suzanne D Burke; Amy McCurley; S Ananth Karumanchi; Iris Z Jaffe Journal: Hypertension Date: 2015-02-23 Impact factor: 10.190
Authors: K H Humphries; M Izadnegahdar; T Sedlak; J Saw; N Johnston; K Schenck-Gustafsson; R U Shah; V Regitz-Zagrosek; J Grewal; V Vaccarino; J Wei; C N Bairey Merz Journal: Front Neuroendocrinol Date: 2017-04-18 Impact factor: 8.333
Authors: Gabor Szalai; Yi Xu; Roberto Romero; Tinnakorn Chaiworapongsa; Zhonghui Xu; Po Jen Chiang; Hyunyoung Ahn; Birgitta Sundell; Olesya Plazyo; Yang Jiang; Mary Olive; Bing Wang; Suzanne M Jacques; Faisal Qureshi; Adi L Tarca; Offer Erez; Zhong Dong; Zoltan Papp; Sonia S Hassan; Edgar Hernandez-Andrade; Nandor Gabor Than Journal: PLoS One Date: 2014-11-13 Impact factor: 3.240