PMID- 7922503
OWN - NLM
STAT- MEDLINE
DCOM- 19941110
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 647
IP  - 2
DP  - 1994 Jun 6
TI  - Agonist-stimulated release of von Willebrand factor and procoagulant factor VIII 
      in rats with and without risk factors for stroke.
PG  - 265-72
AB  - 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-alpha (TNF alpha) 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) 
      +/- TNF alpha 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 affect endothelial cells and make them more 
      responsive to agonist stimulation and thereby increase 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.
FAU - McCarron, R M
AU  - McCarron RM
AD  - Stroke Branch, National Institute of Neurological Disorders and Stroke, National 
      Institutes of Health, Bethesda, MD 20892.
FAU - Doron, D A
AU  - Doron DA
FAU - Siren, A L
AU  - Siren AL
FAU - Feuerstein, G
AU  - Feuerstein G
FAU - Heldman, E
AU  - Heldman E
FAU - Pollard, H B
AU  - Pollard HB
FAU - Spatz, M
AU  - Spatz M
FAU - Hallenbeck, J M
AU  - Hallenbeck JM
LA  - eng
GR  - NS-28225/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Interleukin-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (von Willebrand Factor)
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Animals
MH  - Cerebrovascular Disorders/*metabolism
MH  - Endothelium, Vascular/cytology/metabolism
MH  - Factor VIII/*agonists/*metabolism
MH  - Hypertension/physiopathology
MH  - Injections, Intravenous
MH  - Injections, Intraventricular
MH  - Interleukin-1/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Monocytes/drug effects
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Risk Factors
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - von Willebrand Factor/*agonists/*metabolism
EDAT- 1994/06/06 00:00
MHDA- 1994/06/06 00:01
CRDT- 1994/06/06 00:00
PHST- 1994/06/06 00:00 [pubmed]
PHST- 1994/06/06 00:01 [medline]
PHST- 1994/06/06 00:00 [entrez]
AID - 0006-8993(94)91326-9 [pii]
AID - 10.1016/0006-8993(94)91326-9 [doi]
PST - ppublish
SO  - Brain Res. 1994 Jun 6;647(2):265-72. doi: 10.1016/0006-8993(94)91326-9.