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- Title
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.
- Authors
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
- Abstract
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 PGI2, 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 PGI2 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.
- Subjects
GENE expression; BLOOD platelets; THROMBOXANE synthase; CYCLOOXYGENASES; ENDOTHELIAL cells; XENOTRANSPLANTATION; AORTA physiology; LABORATORY swine
- Publication
Cell Biology International, 2017, Vol 41, Issue 7, p798
- ISSN
1065-6995
- Publication type
Article
- DOI
10.1002/cbin.10782