Activation of human endothelial cells from specific vascular beds induces the release of a FVIII storage pool

Shahani T, Lavend\'homme R, Luttun A, Saint-Remy JM, Peerlinck K, Jacquemin M.
Source: Blood
Publication Date: (2010)
Issue: 115(23): 4902-9
Research Area:
Basic Research
Cells used in publication:
Endothelial, umbilical vein, human (HUVEC)
Species: human
Tissue Origin: vein
Endothelial, MV dermal (HMVEC-d), human
Species: human
Tissue Origin: dermal
Endothelial, aortic, human (HAEC)
Species: human
Tissue Origin: aortic
Endothelial, MV cardiac, human (HMVEC-C)
Species: human
Tissue Origin: heart
Endothelial, pulmonary artery (HPAEC), human
Species: human
Tissue Origin: artery
Endothelial, umbilical artery, human
Species: human
Tissue Origin: extra-embryonic
Although the liver is known to be the main site of factor VIII (FVIII) production, other organs are probably also important for the regulation of FVIII secretion. However, the study of the regulation of extrahepatic FVIII production has been hampered by the lack of definitive identification of human tissues able to secrete FVIII. Recent studies have shown that lung endothelial cells can synthesize FVIII. We therefore studied the production of FVIII by endothelial cells purified from other vascular beds. Because physiologic stress results in a rapid elevation of FVIII, we also investigated whether endothelial cells can store FVIII and secrete it after treatment with agonists. Microvascular endothelial cells from lung, heart, intestine, and skin as well as endothelial cells from pulmonary artery constitutively secreted FVIII and released it after treatment with phorbol-myristate acetate and epinephrine. By contrast, endothelial cells from the aorta, umbilical artery and umbilical vein did not constitutively secrete FVIII or release it after treatment with agonists, probably because of a lack of FVIII synthesis. Extrahepatic endothelial cells from certain vascular beds therefore appear to be an important FVIII production and storage site with the potential to regulate FVIII secretion in chronic and acute conditions.