PMID- 1391943
OWN - NLM
STAT- MEDLINE
DCOM- 19921029
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 80
IP  - 7
DP  - 1992 Oct 1
TI  - Evidence that postoperative fibrinolytic shutdown is mediated by plasma factors 
      that stimulate endothelial cell type I plasminogen activator inhibitor 
      biosynthesis.
PG  - 1758-64
AB  - Postoperative fibrinolytic shutdown has been attributed to an increase in plasma 
      levels of type I plasminogen activator inhibitor (PAI-1) activity and may 
      contribute to postoperative venous thrombosis. The purpose of this study was to 
      determine whether the postoperative increase in PAI-1 is contributed to by a 
      plasma mediator(s) that stimulates PAI-1 synthesis and secretion by vascular 
      endothelium. Plasma samples collected from patients (N = 11) before and after 
      surgery for total hip replacement were (1) assayed for endogenous plasma PAI-1 
      antigen and activity, and (2) incubated with cultured human umbilical vein 
      endothelial cells (HUVECs) and PAI-1 antigen and activity measured in the 
      conditioned medium (CM). Eighteen hours after surgery, endogenous plasma levels 
      of PAI-1 antigen and activity were increased by 225% (P = .003) and 190% (P = 
      .04), respectively over the preoperative values. In addition, compared with 
      preoperative plasma, postoperative plasma increased HUVEC secretion of PAI-1 
      antigen and activity by 99% (P = .001) and 66% (P = .002), respectively. This 
      increase in HUVEC PAI-1 secretion reflects an increase in PAI-1 mRNA expression 
      and protein biosynthesis as confirmed by metabolic radiolabeling, 
      immunoprecipitation, and Northern blot analysis. Ultra-filtration experiments 
      indicate that the postoperative plasma mediator(s) that stimulates HUVEC PAI-1 
      biosynthesis is in a molecular weight (MW) range of approximately 30 to 100 Kd. 
      Heat treatment (56 degrees C; 30 minutes) of postoperative plasma abolished the 
      induction of HUVEC PAI-1 production. Enzyme-linked immunosorbent assay and 
      immunoneutralization experiments indicate that tumor necrosis factor-alpha (TNF 
      alpha) and interleukin-1 alpha (IL-1 alpha) do not contribute to the 
      postoperative plasma effect on HUVEC PAI-1 synthesis. These observations 
      demonstrate that postoperative patient plasma contains a factor(s) that may 
      stimulate endothelial cell PAI-1 biosynthesis in vivo and thus mediate 
      postoperative fibrinolytic shut-down.
FAU - Kassis, J
AU  - Kassis J
AD  - Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
FAU - Hirsh, J
AU  - Hirsh J
FAU - Podor, T J
AU  - Podor TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Interleukin-1)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (RNA, Messenger)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Aged
MH  - Blotting, Northern
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*physiology
MH  - Female
MH  - *Fibrinolysis
MH  - Heparin/therapeutic use
MH  - Hip Prosthesis
MH  - Humans
MH  - Interleukin-1/*blood
MH  - Kinetics
MH  - Male
MH  - Plasminogen Activator Inhibitor 1/*biosynthesis/blood/genetics
MH  - Postoperative Period
MH  - RNA, Messenger/metabolism
MH  - Time Factors
MH  - Umbilical Cord
EDAT- 1992/10/01 00:00
MHDA- 1992/10/01 00:01
CRDT- 1992/10/01 00:00
PHST- 1992/10/01 00:00 [pubmed]
PHST- 1992/10/01 00:01 [medline]
PHST- 1992/10/01 00:00 [entrez]
AID - S0006-4971(20)67541-3 [pii]
PST - ppublish
SO  - Blood. 1992 Oct 1;80(7):1758-64.