Suppression of endothelial t-PA expression by prolonged high laminar shear stress
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- 作者：Erik Ulfhammer ; Maria Carlströ ; m ; Niklas Bergh ; Pia Larsson ; Lena Karlsson ; Sverker Jern
- 关键词：Endothelium ; Shear stress ; Fibrinolysis ; t-PA ; MAPK ; NF-κ ; B
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2009
- 出版时间：6 February 2009
- 年：2009
- 卷：379
- 期：2
- 页码：532-536
- 全文大小：477 K
文摘
Primary hypertension is associated with an impaired capacity for acute release of endothelial tissue-type plasminogen activator (t-PA), which is an important local protective response to prevent thrombus extension. As hypertensive vascular remodeling potentially results in increased vascular wall shear stress, we investigated the impact of shear on regulation of t-PA. Cultured human endothelial cells were exposed to low (1.5 dyn/cm2) or high (25 dyn/cm2) laminar shear stress for up to 48 h in two different experimental models. Using real-time RT-PCR and ELISA, shear stress was observed to time and magnitude-dependently suppress t-PA transcript and protein secretion to approximately 30 % of basal levels. Mechanistic experiments revealed reduced nuclear protein binding to the t-PA specific CRE element (EMSA) and an almost completely abrogated shear response with pharmacologic JNK inhibition. We conclude that prolonged high laminar shear stress suppresses endothelial t-PA expression and may therefore contribute to the enhanced risk of arterial thrombosis in hypertensive disease.