Endothelium, Blood Vessels and Angiogenesis – A Workshop Report
Introduction
The aim of this workshop was to discuss in the broadest terms the role of blood vessels in establishing and maintaining a healthy pregnancy. It focused on the vessels at the feto/maternal interface namely the vessels of chorionic villi and the maternal spiral arteries. Cells of these vessels interact closely with trophoblast cells but with very different outcomes. In the chorionic villi this interaction must work to promote and maintain vessel integrity whilst the interactions between the extravillous trophoblasts and the cells of the maternal spiral artery lead in early pregnancy to vessel instability and remodelling and later vessel stabilisation. Knowledge of the mechanisms behind these paradoxical events may allow new therapeutic approaches to pregnancy complications such as placental insufficiency. The specific questions addressed by organisers and participants included the nature of the interaction between the developing chorionic vascular tree and the chorionic villous trophoblast stem cells, the nature of the interaction between extravillous trophoblasts and the cells of the maternal spiral artery specifically whether apoptosis plays a role in the remodelling of maternal spiral arteries. The role of traditional growth factors such as vascular endothelial growth factor (VEGF) in regulation of maternal and fetal vascular growth and vascular tone was also addressed.
Section snippets
Heterogeneity of endothelial gene expression
The heterogeneity of fetal endothelial cells per se was addressed by Kalionis (Australia) in his talk entitled ‘Homeobox gene expression in placental microvascular endothelial cells’. Using a variation of the perfusion-based method described by Lang et al. [1] placental endothelial cells (PLEC) were isolated by perfusion of the fetal placental vasculature with proteolytic enzymes and enrichment of the cells by Percoll gradient centrifugation. Yields of 5 × 104 to 6 × 105 cells per cotyledon, with
Villous trophoblast–endothelial interactions
Badet (France) addressed the important issue of vasculogenesis within the chorionic villi and whether adjacent cells may influence this. During human placental development, the chorionic villi grow in coordination with the establishment of a large capillary network that occurs by means of both vasculogenesis from in situ differentiating endothelial cells and angiogenesis by sprouting capillaries from pre-existing vessels [3]. Endothelial cells differentiate into blood vessels as a result of
Regulation of maternal and fetal vasculature by placental VEGF
Vascular endothelial growth factor (VEGF) is a well-known angiogenic growth factor and permeability factor. Brownbill (UK) in his talk entitled ‘Placental secretion of VEGF into the fetal land maternal circulations’ introduced the novel concept of the placenta as a major regulatory organ of maternal VEGF endocrinology, as well as being involved as a vasodilator of fetal vessels [9] and in fetal angiogenesis [10], [11] . Data were presented on the measurement of (i) the summated concentrations
Trophoblast–maternal vessel interactions
The second part of the workshop was dedicated to talks on the invading fetal trophoblast cells with cells of the maternal vessels. Rosemary Keogh (UK) and Lynda Harris (UK) addressed the issues of ‘Vascular remodelling in pregnancy’. Keogh, gave an elegant summary of the main features of this interaction. Vascular remodelling of resistance arteries typically involves medial thickening through hyperplasia of smooth muscle cells (SMC) and deposition of extracellular matrix. The result is a
Phenotypic plasticity
As concluding remarks, Leach (UK) cautioned that although micro-heterogeneity may be a feature of endothelial cells in vivo, this was not necessarily due to intrinsic and unchangeable properties of the cell. The environment itself dictates the phenotype. Data were presented showing that when human umbilical vein cells (HUVEC) are grown in a three-dimensional model (trilayer with HUVEC, amnion and retinal pigment epithelial cells) to mimic the outer retinal barrier, HUVEC cells do not show
Conclusions and future directions
This workshop highlighted the need for multi-dimensional human models where different cell types, and their paracrine secretions are allowed to contribute to the final outcome of the experimental stimulus. Rather than reductionist methods alone, such as that provided by cell monocultures, the use of more complex ex vivo and in vitro models such as the extra-corporeally perfused human placenta, the co-cultures and trilayers may well lead the way in this complex and important field of
Acknowledgements
The authors would like to thank Action Research (PB), the Anatomical Society of Great Britain and Ireland, the MRC (LL), the INSERM, the Lynne Quayle Charitable Trust Fund (Equity Trustees), the Marian and EH Flack Trust (BW), and the Wellcome Trust (LH, RK, LL).
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2021, Vitamins and HormonesCitation Excerpt :Human spiral arteries comprise a single endothelial layer upon an elastic lamina surrounded by vascular smooth muscle cells with the associated extracellular matrix. These strained and rigid coiled-appearance vessels are transformed into larger, low-resistance vessels that allow the significant increase in blood flow detailed before (Demir, Yaba, & Huppertz, 2010; Harris et al., 2006; Leach et al., 2006). As a result of the spiral artery remodeling, vascular resistance decreases.
The role of homeobox genes in the development of placental insufficiency
2012, Fetal Diagnosis and Therapy