Changes in tissue content and hepatic clearance of tissue-type plasminogen activator during diet-induced hyperlipidaemia in rats
article
Hyperlipidaemia was induced in rats by feeding a diet enriched with butter (40% w/w) and cholesterol (5% w/w), and supplemented with thiouracil (0.3% w/w). As has been demonstrated previously, this treatment induces increased plasma levels of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) activity. In the present study plasma levels of von Willebrand factor (vWF) were also found to be increased. The tissue concentration t-PA and its clearance from the blood were compared in the hyperlipidaemic rats and in normolipidaemic control rats. t-PA activity and antigen were measured in lung, heart, kidney and liver after extraction with acid acetate-buffer or with KSCN-buffer, and were found to be similar in the tissue extracts of hyperlipidaemic and control rats. Plasma t-PA clearance was measured in both groups of rats in vivo, while the efficacy of the liver in extracting t-PA was analysed using an ex vivo liver perfusion system. The in vivo clearance study showed that the half-life of t-PA was significantly prolonged in hyperlipidaemic rats (83 ± 9 s) compared with control rats (58 ± 6 s). In the liver perfusion experiments, the extraction of t-PA from the perfusate was smaller in the hyperlipidaemic group (48 ± 5%) than in the control rats (60 ± 8%). Together the data suggest that the increased plasma level of t-PA in hyperlipidaemic rats may be due to decreased liver clearance.
TNO Identifier
231952
ISSN
02689499
Source
Fibrinolysis, 6(4), pp. 250-255.
Pages
250-255
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