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The roles of thrombomodulin, protein C, and activated protein C in endothelial cell proliferation
Author(s) -
Bennett Kristen,
Teigland Chris,
Glasscock Laura Neese
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a656-d
Subject(s) - thrombomodulin , protein c , microbiology and biotechnology , chemistry , cell growth , biology , biochemistry , immunology , thrombin , platelet
We determined the effects of protein C and activated protein C (APC) on human umbilical vein endothelial cell (HUVEC) proliferation in the presence and absence of thrombomodulin (TM). TM bound to thrombin activates protein C into APC. Previous studies show that thrombin increases the mitogenic activity of HUVEC, an activity that is blocked when thrombin binds to TM, and that APC induces HUVEC proliferation through the protein C receptor (EPCR). We investigated the effects of protein C and APC on HUVEC proliferation in the presence and absence of TM. HUVEC were exposed to purified thrombin, protein C and APC in the presence and absence of antibody to TM and the amount of proliferation was determined. In the presence of TM, protein C decreased and APC increased HUVEC proliferation. In the absence of TM, HUVEC proliferation decreased in the absence of protein C, APC, or thrombin, increased in the presence of thrombin, decreased in the presence of protein C, and increased in the presence of APC. In the absence of TM, protein C was not activated by the TM‐thrombin complex and the increase in proliferation seen by the addition of purified APC was abolished. In conclusion, blocking TM cell surface expression decreases the APC‐induced increase in HUVEC proliferation. Supported by NIH IDeA Networks of Biomedical Research Excellence, McKay Urology Endowment Fund and the Foundation for the Carolinas.