Agonist-stimulated release of von Willebrand factor and procoagulant factor VIII in rats with and without risk factors for stroke

Richard M. McCarron, David A. Doron, Anna Leena Sirén, Giora Feuerstein, Eliahu Heldman, Harvey B. Pollard, Maria Spatz, John M. Hallenbeck

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Lipopolysaccharide (LPS)-induced (i.v. or i.c.v., 1.8 mg/kg) release of von Willebrand factor (vWF) was examined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. SHR rats released significantly (P < 0.05) more vWF than WKY rats in response to LPS. LPS also inhibited factor VIII procoagulant activity (FVIII: c) which may indicate an increase in thrombin activity. Cultured cerebrovascular endothelial cells (EC) derived from both SHR and WKY rats, as well as human umbilical vein EC (HUVEC) cultures constitutively released vWF. Treatment with agonists including LPS, thrombin and tumor necrosis factor-α (TNFα) did not affect the in vitro secretion of vWF by cerebrovascular EC cultures but significantly upregulated vWF release by HUVEC cultures. Preincubation of cerebrovascular EC cultures with interleukin-1 (IL-1) ± TNFα or co-culturing in the presence of LPS-activated syngeneic monocytes had no effect on vWF secretion. The findings demonstrate that conditions of hypertension may effect endothelial cells and make them more responsive to agonist stimulation and thereby increaase secretion of vWF, an important factor in hemostasis as well as thrombosis. The capacity of LPS to significantly affect the in vivo secretion of vWF in SHR and WKY rats but not cultured cerebrovascular EC indicates that observed elevations in plasma vWF were not derived from cerebrovascular EC. It is suggested that hypertension may function as a risk factor for thrombotic stroke by influencing factors involved in coagulation processes, such as vWF and factor VIII:c.

Original languageEnglish
Pages (from-to)265-272
Number of pages8
JournalBrain Research
Issue number2
StatePublished - 6 Jun 1994
Externally publishedYes


  • Endothelial cell
  • Hypertension
  • Lipopolysaccharide
  • Monocyte
  • Stroke
  • von Willebrand factor

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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