Changes in signal transduction in the platelets of patients with peripheral occlusive arterial disease.
BACKGROUND
The finding that platelets of patients with peripheral occlusive arterial disease (POAD) circulate in an activated state prompted us to study platelet signal transduction. We hypothesised that platelet hyperreactivity is caused by changes in intracellular signalling.


METHODS



METHODS
a single blood sample was taken from the antecubital vein of each participant prior to the start of intravenous treatment with prostaglandins.


METHODS
patients were recruited from our inpatient Department of Cardiology and Angiology at the University Hospital.


METHODS
15 hospitalised patients with symptomatic POAD were randomly selected. Patients receiving antiplatelet drugs and those with diabetes were excluded. The control group consisted of 15 healthy volunteers from the medical staff.


METHODS
blood tests were performed on the day of admission before any therapeutic intervention.


METHODS
the platelet activation marker P-selectin was quantified on peripheral blood platelets before and after in vitro stimulation with platelet agonists (adenosine diphosphate, thrombin receptor activator peptide-6). The signal transduction cascade was also selectively blocked by preincubation with either: 1) forskolin, 2) phospholipase C inhibitor U-73122, or 3) bisindolylmaleimide.


RESULTS
A stronger inhibitory effect on ADP-stimulated platelets was seen in patients with U-73122, as indicated by a decrease in mean fluorescence intensity of 51% versus 34% in controls (p<0.0005).


CONCLUSIONS
Our findings support the assumption that changes in platelet signal transduction in POAD lead to platelet hyper-reactivity.
Woinke
M
M
Department of Cardiology-Angiology, Medical Hospital I, University of Leipzig, Germany.
Zeiger
F
F
Ruehlmann
C
C
Pfeiffer
D
D
Koksch
M
M
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001157:Arterial Occlusive Diseases / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011506:Proteins; D011760:Pyrrolidinones / Q000494:pharmacology; D018179:Receptors, Thrombin; D015290:Second Messenger Systems; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D004963:Estrenes; D007211:Indoles; D008301:Maleimides; D019007:P-Selectin; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011506:Proteins; D011760:Pyrrolidinones; D018179:Receptors, Thrombin; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D005576:Colforsin; D000244:Adenosine Diphosphate; C088060:bisindolylmaleimide