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Thrombin generation by apoptotic vascular smooth muscle cells
PD Flynn, CD Byrne, TP Baglin, PL Weissberg and MR Bennett
Department of Medicine, Addenbrooke's Hospital, Cambridge, UK.
Thrombin activation requires assembly of a prothrombinase complex of
activated coagulation factors on an anionic phospholipid surface,
classically provided by activated platelets. We have previously shown that
anionic phosphatidylserine is exposed by rat vascular smooth muscle cells
(VSMCs) undergoing apoptosis after serum withdrawal. In this study, using a
chromogenic assay, we have shown thrombin generation by apoptotic VSMCs
expressing c-myc (VSMC-myc) with an area under the thrombin-generation
curve (AUC) of 305 +/- 17 nmol x min/L and a peak thrombin (PT) of 154 +/-
9 nmol/L. The thrombin-generating potential of the apoptotic VSMC-myc cells
was greater than that of unactivated platelets (P = .003 for AUC; P = .0002
for PT) and similar to calcium-ionophore activated platelets (AUC of 332
+/- 15 nmol x min/L, P = .3; PT of 172 +/- 8 nmol/L, P = .2). Thrombin
activation was also seen with apoptotic human VSMCs (AUC of 211 +/- 8 nmol
x min/L; PT of 103 +/- 4 nmol/L) and was inhibited by annexin V (P <
.0001 for AUC and PT). VSMC-myc cells maintained in serum generated less
thrombin than after serum withdrawal (P = .0002 for AUC and PT). VSMCs
derived from human coronary atherosclerotic plaques that apoptose even in
serum also generated thrombin (AUC of 260 +/- 2 nmol x min/L; PT of 128 +/-
4 nmol/L). We conclude that apoptotic VSMCs possess a significant
thrombin-generating capacity secondary to phosphatidylserine exposure.
Apoptotic cells within atherosclerotic plaques may allow local thrombin
activation, thereby contributing to disease progression.
Volume 89,
Issue 12,
pp. 4378-4384,
06/15/1997
Copyright © 1997 by The American Society of Hematology
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