T. Padro et al., TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND ITS INHIBITOR IN RAT AORTA - EFFECT OF ENDOTOXIN, Arteriosclerosis and thrombosis, 14(9), 1994, pp. 1459-1465
Plasminogen activator (PA) and PA inhibitor (PAI) antigen, activity, a
nd mRNA were analyzed in the three layers of rat aorta, and the effect
of endotoxin on PA and PAI was studied. All PA activity in aorta was
identified as tissue-type PA (TPA) activity; no urokinase-type PA was
detected. In the tunica adventitia TPA activity, TPA antigen, and TPA
mRNA were detected, whereas in the tunica media TPA antigen and TPA mR
NA, but no TPA activity, were found. PAI activity was detected in the
tunica media, explaining the absence of TPA activity in this layer. Re
moval of the endothelial cells had no effect on TPA antigen and PAI ac
tivity in intima-media preparations. Also, similar amounts of PAI-1 mR
NA were found in intima-media preparations, irrespective of the presen
ce or absence of the intima. Immunohistochemical staining showed that
TPA immunoreactivity was present in all three layers of the aorta, whe
reas PAI-1 immunoreactivity was found in medial smooth muscle cells bu
t not in endothelial cells. After endotoxin treatment, TPA activity wa
s decreased in extracts of the total aorta and of the adventitia, alth
ough TPA antigen and TPA mRNA were unchanged. PAI-1 mRNA was strongly
increased in the tunica adventitia and in the tunica media, as was PAI
activity in the tunica media. Thus, endotoxin decreased TPA activity
by increasing the synthesis of PAI-1; TPA was unaffected. Our observat
ions in rat aorta differ from observations in mouse aorta and in rat c
arotid artery, and they caution against extrapolation from one tissue
(or species) to another.