Journal
CARDIOVASCULAR RESEARCH
Volume 93, Issue 1, Pages 152-161Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvr276
Keywords
Trophoblast; Endothelial Cell; Migration; Adhesion molecules; Shear stress
Categories
Funding
- New Zealand Foundation of Science and Technology [SGRG0701]
- Royal Society
- St George's University of London
Ask authors/readers for more resources
Aims In early human pregnancy placental trophoblasts migrate along uterine spiral arteries (SAs) and remodel these vessels into wide-bore conduits in a process essential for successful pregnancy. Until 10-12 weeks gestation trophoblasts plug spiral arteries, resulting in slow, high-resistance blood flow. This work examined the consequences of these low shear stress conditions on trophoblast migration, adhesion molecule expression, and attraction to chemotactic factors. Methods and results Trophoblasts were cultured on fibronectin or human endothelial cells for 6-12 h under 0.5-6 dyne/cm(2) shear stress using the BioFlux200 system, and imaged by time-lapse microscopy. Computer-based imaging algorithms were developed to automatically quantify migration. Chemotaxis assays were run using parallel flow. Trophoblasts cultured on fibronectin or endothelial cells did not undergo directional migration in 0.5 and 2 dyne/cm(2) cultures; however, in 4 and 6 dyne/cm(2) trophoblasts migrated with the direction of flow (n = 4, P < 0.001). Shear stresses did not affect the speed of trophoblast migration, or adhesion molecule expression (E-selectin, alpha(4), beta(1), and alpha(v)beta(3) integrin). Trophoblasts cultured on endothelial cells migrated into media containing interleukin-8, macrophage chemoattractant protein-1, or Regulated-upon-Activation-Normal-T-cell-Expressed-and-Secreted (RANTES) (n = 5, P < 0.05). Conclusions Shear stress increases trophoblast migration in the direction of flow, challenging the idea that trophoblasts migrate down spiral arteries retrograde to flow. This suggests that low shear stresses generated by trophoblast plugging of spiral arteries in the first trimester may favour arterial remodelling by preventing the migration with flow seen at higher shear stresses, allowing trophoblasts to migrate down the arteries in response to alternate stimuli such as uterine or endothelial cell-derived chemotactic factors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available