Cellular and Molecular Regulation of Spiral Artery Remodelling: Lessons from the Cardiovascular Field

Abstract

A number of important changes take place in the maternal uterine vasculature during the first few weeks of pregnancy resulting in increased blood flow to the intervillous space. Vascular endothelial and smooth muscle cells are lost from the spiral arteries and are replaced by fetal trophoblast cells. Failure of the vessels to remodel sufficiently is a common feature of pregnancy pathologies such as early pregnancy loss, intrauterine growth restriction and pre-eclampsia. There is evidence to suggest that some vascular changes occur prior to trophoblast invasion, however, in the absence of trophoblasts remodelling of the spiral arteries is reduced. Until recently our knowledge of these events has been obtained from immunohistochemical studies which, although extremely useful, can give little insight into the mechanisms involved. With the development of more complex in vitro models a picture of events at a cellular and molecular level is beginning to emerge, although some caution is required in extrapolating to the in vivo situation. Trophoblasts synthesise and release a plethora of cytokines and growth factors including members of the tumour necrosis factor family. Studies suggest that these factors may be important in regulating the remodelling process by inducing both endothelial and vascular smooth muscle cell apoptosis. In addition, it is evident from studies in other vascular beds that the structure of the vessel is influenced by factors such as flow, changes in the composition of the extracellular matrix, the phenotype of the vascular cells and the local immune cell environment. It is the aim of this review to present our current knowledge of the mechanisms involved in spiral artery remodelling and explore other possible pathways and cellular interactions that may be involved, informed by studies in the cardiovascular field.

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

“…Multiple mechanisms contribute to the structural changes of spiral arteries including extracellular matrix restructuring, endothelial and smooth muscle cell de-differentiation, migration and proliferation, changes in cell adhesion and sensitivity to death-inducing stimuli. 10,39,40 The positioning and localized delivery of IFNG by uNK cells in support of any of these processes may be inappropriate or insufficient in B6.Ly49 KD to effect remodelling. Alternatively, other cell types may be compensating sources of IFNG in B6.Ly49 KD , and not properly localized to be effective in driving this remodelling.…”

Ecto-nucleotidases distribution in human cyclic and postmenopausic endometrium

“…Spiral artery remodeling plays a central role in establishing and maintaining a normal pregnancy, and impaired remodeling is involved in common pregnancy disorders such as recurrent pregnancy loss and pre-eclampsia, a major complication of pregnancy and one of the leading causes of maternal and perinatal morbidity and mortality. In spite of the obvious importance, very little is known of the mechanisms responsible for this remodeling, and characterizing these arteries phenotypically has important implications for this understanding [44,45].…”

The placenta: a multifaceted, transient organ

“…The remodelling process involves the loss of smooth muscle cells from the walls of the spiral arteries, either through dedifferentiation or apoptosis, and their replacement by an inert, amorphous fibrinoid material [38,39]. The molecular mechanisms involved are still unclear, but it is now recognized that there is an initial phase of endocrine priming followed by a second phase that is dependent on the presence of extravillous trophoblast cells [40,41].…”