Endothelial Cells: Master Regulators of Vascular Function

Endothelial cells line blood vessels and are crucial for maintaining proper vessel homeostasis and blood flow. They are essential for regulating thrombosis (blood clotting), vessel growth, and angiogenesis (formation of new blood vessels).

The molecular crosstalk between endothelial cells and factors in the blood and vessels regulates endothelial cell function. Factors in the blood or changes in blood flow or pressure can activate endothelial cells. In response, endothelial cells secrete various signal mediators, including nitric oxide, which causes vessel dilation.

Endothelial cells also respond to vessel damage by inducing thrombosis to prevent blood loss. Endothelial cells release platelet-activating factor or thrombin, which recruit and activate platelets to form a blood clot. Given their critical role in vascular function, endothelial cell dysregulation can have detrimental effects, leading to conditions such as atherosclerosis, hypertension, and inflammation.

Endothelial cells have been extensively studied in vitro to gain insights into both normal and pathogenic vascular states. In particular, the role of endothelial cells in angiogenesis can be modeled in vitro using a tube formation assay, where endothelial cells, such as Human Umbilical Vein Endothelial Cells (HUVECs), migrate and organize into vessel-like structures when grown on a basement membrane matrix with stimulation from pro-angiogenic factors, including VEGF. Lifeline® provides endothelial cells that have been used in these types of studies.

Lifeline® HUVECs: An In Vitro Model of Angiogenesis

Prostate-specific membrane antigen (PSMA) expression is often elevated in prostate cancer and has been used as a biomarker for prostate cancer. Interestingly, PSMA expression has been reported in the neovasculature of other cancer types, but is absent from normal vasculature.

Liu et al. used an in vitro system to investigate the induction of breast cancer-associated endothelial PSMA expression and angiogenesis. They grew Lifeline® HUVECs in Matrigel in the presence of conditioned medium from MDA-MB-231 and MCF-7 breast cancer cells, using the ability of HUVECs to form vessel-like tubes as an assay for angiogenesis. They found that conditioned medium from the more aggressive breast cancer cell line, MDA-MB-231, resulted in tube formation that was accompanied by expression of PSMA; MCF-7-conditioned medium did not induce HUVEC tube formation. These results indicate that at least one type of breast cancer cell has the ability to induce angiogenesis with endothelial PSMA expression; future studies will further define the mechanism by which this occurs and whether other cancer cell types can induce a similar PSMA-associated endothelial angiogenesis phenotype.

Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), prevents the angiogenic and growth-promoting activities of VEGF, which aid in tumor metastatic spread. Yang et al. tested the efficacy of bevacizumab in uveal melanoma cells to determine whether bevacizumab could be a potential therapeutic strategy for uveal melanoma. The authors used Lifeline® Human Umbilical Vein Endothelial Cells (HUVECs) to evaluate the effect of bevacizumab on vascular endothelial cells. They found bevacizumab treatment decreased VEGF secretion by HUVECs. In addition, bevacizumab-treated HUVECs exhibited a decreased angiogenic phenotype in vitro. Finally, in an in vivo mouse model of uveal melanoma, bevacizumab decreased angiogenesis and proliferation. These results suggest that bevacizumab could be a viable therapy in uveal melanoma.

Lifeline® offers two types of HUVECs:

• HUVECs from individual donors (isolated from human umbilical cord and cryopreserved as primary cells)
• HUVECs from a 10-donor pool (isolated from human umbilical cord and cryopreserved as secondary cells)

Lifeline® HUVECs can be grown in Lifeline® VascuLife media, VascuLife EnGS Medium (a formulation without VEGF) and form capillary tubes and vessel-like networks when grown in VascuLife VEGF Medium.

Lifeline® HUVECs can be used to study:

• Normal endothelial cell biology and angiogenesis
• Tumor angiogenesis
• Cancer cell metastasis
• Immune cell transmigration
• Wound healing
• Endothelial cell stiffness
• Atherosclerosis

Tell us how you are using Lifeline® HUVECs and your research study could be featured here on our blog!