The cardiovascular system is an extensive network that supports blood flow to the tissues of the body. Blood vessels have a specialized lining of endothelial cells that not only regulate vessel homeostasis, but also form a protective barrier between factors in the blood and the internal environment. They have substantial migratory ability and also participate in wound healing. Since endothelial cells are the primary messenger between the blood and the internal environment, it is crucial that they function properly. Multiple disease conditions are caused or exacerbated by endothelial dysfunction, including atherosclerosis, cardiovascular disease, diabetes, and more. The following studies use Lifeline® endothelial cells to study the role of endothelial cells in atherosclerosis and vascular patterning during development.
Recent Research Using Lifeline® Endothelial Cells to Study Atherosclerosis and Vascular Development
In a 2015 study, Evani et al. investigated the role of Chlamydia pneumoniae in atherosclerosis. Previous studies have shown that C. pneumoniae infection is correlated with host changes that induce atherosclerosis, but the mechanism is unclear. They hypothesized that following monocyte infection, C. pneumoniae infection promotes atherosclerosis by changing endothelial-monocyte interactions.
The researchers used Lifeline® primary human aortic endothelial cells (HAECs) to study why C. pneumoniae-infected monocytes displayed altered rolling behavior when exposed to endothelium. They found that infected monocytes rolled more uniformly and slower than uninfected control cells, had less fluid membranes, and displayed different lipid raft properties. E-selectin is an important endothelial receptor that mediates monocyte adhesion to the endothelium. In this study, the group showed that CD44 is the primary E-selection co-receptor on monocytes, and C. pneumoniae infection causes redistribution of CD44 out of lipid rafts. Additionally, in hyperlipidemia conditions (high LDL), infected monocytes experience a further increase in membrane fluidity and decrease in rolling speed. Finally, the researchers illustrate that infected monocytes exposed to LDL switch from rolling to fixed adhesion more often than uninfected cells. Together, the results of this study establish the link between C. pneumoniae infection and the first stage of atherosclerosis, adhesion of monocytes to the endothelium.
Aghajanian et al. set out to determine the mechanisms behind the formation of coronary venous connections during development. In particular, they were interested in the role of class 3 semaphorins (Sema3), secreted guidance molecules that play a role in vascular patterning. Using Sema3d-/- mice, they found that Sema3d is required for formation of coronary venous connections, but not coronary arterial connections. To determine how Sema3d is involved in forming these connections and how it signals to endothelial cells to stimulate migration, the researchers used Lifeline® human umbilical vein endothelial cells (HUVECs) in migration assays. They identified ErbB2 receptor tyrosine kinase 2 (ErbB2) as a potential candidate for interaction with Sema3d, and found that Sema3d inhibited HUVEC migration, an effect that was prevented upon ErbB2 knockdown.
The researchers validated these observations in vivo, demonstrating that Sema3d and ErbB2 signaling interactions are important for proper heart development. Furthermore, the group demonstrated that ErbB2 and the Sema3 co-receptor, neurophilin 1 (Nrp1) interact to form a signaling complex in HUVECs. Together, the results of this study implicate ErbB2 in a new role in heart development and tissue patterning.
Lifeline® endothelial cells, optimized for growth in VascuLife® medium, are available from multiple sources, including:
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