Objectives: Individuals delivered from preeclamptic pregnancies exhibit a long-term increased risk of developing cardiovascular and metabolic diseases, likely caused by aberrant fetal cell reprogramming incurred in utero. The present study investigated the functional impairment and epigenetic changes exhibited by endothelial progenitor cells derived from offspring born to preeclamptic pregnancies. Study design: The capacity of CD133 + /C-kit + /Lin − (CKL − ) human umbilical cord blood endothelial progenitor cells (EPCs) derived from gestationally matched normal and preeclamptic (n = 10 each) pregnancies to differentiate to form outgrowth endothelial cells (OECs) was assessed by observing both their morphology, and the number and size of generated OECs colonies. Likewise, OECs angiogenic function was evaluated via migration, adhesion, and tube-formation assays. EPCs from preeclampsia were cultured in normal-, and preeclampsia-derived serum-conditioned media to assess the effects of environmental factors on EPC differentiation potency and OEC angiogenic function, and finally, EPCs H3K4, H3K9, and H3K27 trimethylation levels were assayed. Results: The preeclampsia-derived CKL − EPCs exhibited decreased H3K4 and H3K9 trimethylation levels, significantly delayed differentiation times, and a significant reduction in both their number of generated OECs colonies, and exhibited reduced OECs migration, adhesion, and tube formation activities compared to those achieved by the normal-derived EPCs. Interestingly, the reduced differentiation potency of the preeclampsia-derived EPCs was not rescued via exposure to normal serum. Conclusions: Exposure to preeclampsia significantly and irreversibly reduced CKL − EPC differentiation potency and OEC angiogenic function, likely reflecting incurred irreversible epigenetic changes.
Bibliographical noteFunding Information:
This research was supported by a Basic Science Research Program grant (NRF-2017R1D1A1B03029081, and NRF-2016R1D1A1B03933337) awarded by the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education. Support was also provided by the Stem Cell Therapy Research Foundation , which is funded by Sung-Il Roh from the Mizmedi Hospital, Seoul, Korea. And this research was also supported by a National Research Foundation of Korea (NRF-2017R1C1B5076378) grant funded by the Ministry of Science and IT (MSIT).
All Science Journal Classification (ASJC) codes
- Internal Medicine
- Obstetrics and Gynaecology