Placental ischemia due to inadequate remodeling of the uterine spiral arteries (uSpAs) is the key for the preeclampsia (PE) development. Remodeling of uSpAs is essentially a program of vascular injury-repair, implying endothelial progenitor cells (EPCs) play a crucial role in the establishment of utero-placental circulation. Here we identified down-regulation of AMPK phosphorylation in blood outgrowth endothelial cells (BOECs) and lineage-CD117highKDRhigh of PE. Deficient-AMPK promoted excessive sEng secretion via HO-1 inhibition in EPCs, which impaired remaining endothelium and induced accumulation of ECM produced by VSMCs in remodeling uSpAs. Synthetic phenotype transition is obvious in VSMCs of PE uSpAs depending on TGF-β1 signaling and sEng from EPCs turned out to be a considerable agent in that transition. Both pregnant mice exogenously transplanted with BOECs of PE and model constructed into AMPK-deficiency specific in endothelium within bone marrow manifested preeclamptic phenotypes with appearance of prelabeled EPCs in remodeling uSpAs with stenosis. Thus, our findings support that EPCs narrow remodeled uSpAs with hyporeactivity leading to utero-placental low-perfusion, which is the promising pathogenesis of PE.