In breakthrough research, Rice University (RU) scientists have uncovered more about the cellular origins of factor VIII (FVIII), a protein that plays a critical role in the blood clotting process. The study paper was co-authored by research biochemist Nancy A. Turner, BA, and hematologist Joel L. Moake, MD, at RU’s Department of Bioengineering.
Earlier studies established that FVIII is produced in endothelial cells that line the walls of blood vessels in organs such as the heart, liver and intestines. RU investigators have delved further by looking for the specific source of FVIII generation and deployment from within different types of endothelial cells.
Turner and Moake’s experiments focused on human umbilical vein endothelial cells (HUVECs)’ which are found in large veins, and glomerular microvascular endothelial cells (GMVECs), which are located in the smallest capillaries of the kidneys. Although the presence of FVIII in these types of cells had not been previously confirmed, investigators had recognized them, particularly HUVECs, as a viable focus of research for several reasons.
“HUVECs are the generic human endothelial cells that (biological researchers) use the first time they do anything,” Turner said. “They’re cheap. They’re easy to work with, and they’ve been the model for endothelial cells for, I don’t know, at least 50 years.”
With her expertise in biochemistry, Turner first conducted a series of lab tests to verify the presence of FVIII in HUVECs and GMVECs. Follow-up research confirmed that FVIII is not only synthesized in HUVECs and GMVECs, but is also stored in and secreted from Weibel-Palade bodies (WPBs) within these cells. WPBs are specialized organelles (part of a cell with a specific function) that also contain von Willebrand factor (VWF), another critical protein that binds to FVIII during the clotting cascade. VWF works as a carrier for FVIII as it circulates in the bloodstream.
This discovery has future potential therapeutic significance for people with bleeding disorders. “Now that we recognize that factor VIII is normally synthesized in endothelial cells and stored in Weibel-Palade bodies, those become the precise, most effective physiological targets for gene delivery,” concluded Moake.
The article, “Factor VIII Is Synthesized in Human Endothelial Cells, Packaged in Weibel-Palade Bodies and Secreted Bound to ULVWF Strings,” was published online October 16, 2015, in the journal PLOS ONE.
Source: Rice University news release dated November 2, 2015