Physiological Smooth Muscle Cell Apoptosis Contributes to the Uterine Vascular Remodeling in Human Early Pregnancy

Abstract

See related article, pages 834–841 Although equipped with the entire machinery driving cell proliferation and cell death, the turnover of the vascular smooth muscle cell (VSMC) layer within the vascular wall is quite low throughout the adult normal body. Vascular wall remodeling with VSMC apoptosis is routinely considered as associated with vascular diseases. This includes the development and regression of vascular thickening in hypertension, in advanced atherosclerotic plaques where VSMC apoptosis promotes plaque rupture, after angioplasty-induced arterial injury, as well as in arterial aneurysm where apoptosis is responsible for excessive slackening and rupture of the vessel media.1 Furthermore, in several animal studies, early pregnancy is a physiological situation where vessel wall remodeling plays a vital role. Indeed, in the first trimester of human pregnancy, vascular wall remodeling through degenerative changes converts the uterine spiral arteries located within the decidua basilis into toneless, widely opened arteries, thus enabling abundant blood supply to the maternal-fetal exchange area within the placenta. It is known that extravillous cytotrophoblasts deriving from fetal cytotrophoblastic shell migrate into segments of the spiral artery wall, through retrograde endovascular (intravasation) and interstitial migratory pathways (extravasation) into the decidua basilis to trigger the disappearance of endothelial and VSMC. In this process, trophoblasts become buried intramurally within a fibrinoid layer, which replaces the original muscular medial layer. Such trophoblast invasion converts the ends of spiral arteries into a wide caliber vessel that can better deliver maternal blood to the expanding intervillous space of the placenta (Figure 1A). Defective or incomplete trophoblast invasion can result in pathological pregnancies, including preeclampsia and intrauterine growth restriction.2,3 Therefore, understanding the cellular mechanisms governing the interaction between intramural trophoblast and vascular wall cells is yet to be determined. Oversimplified schematic depicting the trophoblasts invading the spiral artery traveling from myometrium up to …