Doctor of Philosophy
Heparin, which is a glycosaminoglycan, was originally found and used as an anti-coagulant. But it has also been implicated in binding to vascular cells, down-regulating their proliferation and inflammation responses at least through MAPK pathways ,  by employing the PKG pathway . Previous studies have indicated that heparin increases eNOS(endothelial nitric oxide synthase) activity in bovine endothelial cells. However, the precise mechanism has not been fully elucidated.Immunoprecipitation in endothelial cells by using monoclonal heparin binding blocking antibodies identified a protein as a gene product of TMEM184A, to be a putative heparin receptor .In this study, we investigated the impact of heparin treatment on eNOS's activation and the role of eNOS in heparin signaling. The results indicate that heparin induced phosphorylation and activation of eNOS. eNOS was internalize to perinuclear region in a TMEM184A dependent manner in response to heparin. We also examined how heparin treatment lead to phosphorylation of eNOS and confirmed that TMEM184A and Ca2+ were required to mediate heparin elicited eNOS phosphorylation. Integrin and TRPV4 are demonstrated to be potentially involved in this activation process on eNOS.
Li, Yaqiu, "eNOS and TMEM184A in Heparin Signaling effects on Vascular Cells" (2018). Theses and Dissertations. 5606.