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Altered expression of eNOS, prostacyclin synthase, prostaglandin G/H synthase, and thromboxane synthase in porcine aortic endothelial cells after exposure to human serum—relevance to xenotransplantation
Author(s) -
Chen Pengfei,
Gao Hanchao,
Lu Ying,
Nie Huirong,
Liu Zhaoming,
Zhao Yu,
Fan Nana,
Zou Qingjian,
Dai Yifan,
Tang Aifa,
Hara Hidetaka,
Cai Zhiming,
Cooper David K.C.,
Lai Liangxue,
Mou Lisha
Publication year - 2017
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10782
Subject(s) - thromboxane a synthase , prostacyclin , enos , nitric oxide synthase , xenotransplantation , prostaglandin h2 , platelet , thromboxane , atp synthase , medicine , nitric oxide synthase type iii , endothelium , platelet activation , endocrinology , prostaglandin , thromboxane a2 , prostanoid , chemistry , biology , nitric oxide , transplantation , biochemistry , enzyme
Under normal conditions, the activity of platelets is stringently and precisely balanced between activation and quiescent state. This guarantees rapid hemostasis and avoids uncontrolled thrombosis. However, excessive platelet activation and resulting thrombotic microangiopathy are frequently observed in pig‐to‐primate xenotransplantation models. Endothelium‐derived inhibitory mechanisms play an important role in regulation of platelet activation. These mainly include nitric oxide (NO), prostacyclin PGI 2 , and adenosine, which are synthesized by endothelial NO synthases (eNOS), prostacyclin synthase, and CD39/CD73, respectively. We investigated whether endothelium‐derived regulatory mechanisms are affected in porcine aortic endothelial cells (PAECs) after exposure to human serum. In the present study, exposure of PAECs or porcine iliac arteries to human serum suppressed gene expression of eNOS and prostacyclin synthase, while induced gene expression of prostaglandin G/H synthase and thromboxane synthase. Simultaneously, exposure to human serum reduced NO and PGI 2 production in PAEC culture supernatants. Thus, human serum altered the balance of endothelium‐derived inhibitory mechanisms in PAECs, which may indicate a regulatory mechanism of excessive platelet activation in pig‐to‐primate xenotransplantation.