Endothelial progenitor cells control remodeling of uterine spiral arteries for the establishment of utero-placental circulation.

Placental ischemia, resulting from inadequate remodeling of uterine spiral arteries, is a factor in the development of preeclampsia. However, the effect of endothelial progenitor cells that play a role in the vascular injury-repair program is largely unexplored during remodeling. Here, we observe that preeclampsia-afflicted uterine spiral arteries transition to a synthetic phenotype in vascular smooth muscle cells and characterize the regulatory axis in endothelial progenitor cells during remodeling in human decidua basalis. Excessive sEng, secreted by AMP-activated protein kinase (AMPK)-deficient endothelial progenitor cells through the inhibition of HO-1, damages residual endothelium and leads to the accumulation of extracellular matrix produced by vascular smooth muscle cells during remodeling, which is further confirmed by animal models. Collectively, our findings suggest that the impaired functionality of endothelial progenitor cells contributes to the narrowing of remodeled uterine spiral arteries, leading to reduced utero-placental perfusion. This mechanism holds promise in elucidating the pathogenesis of preeclampsia. [Display omitted] • Endothelial progenitor cells control uterine spiral artery (uSpA) remodeling • CD117highKDRhigh cells with AMPK deficiency release excessive sEng via HO-1 inhibition • Excessive sEng induces stenosis in remodeled uSpAs Tan et al. demonstrate that the suppressive AMPK/HO-1 regulatory axis in endothelial progenitor cells overproduces sEng, which contributes to the narrowing of remodeled uterine spiral arteries. The mechanism holds promise in elucidating the pathogenesis of preeclampsia. [ABSTRACT FROM AUTHOR]