Suppression of endothelial t-PA expression by prolonged high laminar shear stress

Erik Ulfhammer, Maria Carlström, Niklas Bergh, Pia Larsson, Lena Karlsson, Sverker Jern

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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.

Original languageEnglish
Pages (from-to)532-536
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 6 Feb 2009
Externally publishedYes


  • Endothelium
  • Fibrinolysis
  • MAPK
  • NF-κB
  • Shear stress
  • t-PA

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