Tissue-type plasminogen activator and its inhibitor in rat aorta. Effect of endotoxin.

Abstract

Plasminogen activator (PA) and PA inhibitor (PAI) antigen, activity, and 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 mRNA, but no TPA activity, were found. PAI activity was detected in the tunica media, explaining the absence of TPA activity in this layer. Removal of the endothelial cells had no effect on TPA antigen and PAI activity in intima-media preparations. Also, similar amounts of PAI-1 mRNA were found in intima-media preparations, irrespective of the presence or absence of the intima. Immunohistochemical staining showed that TPA immunoreactivity was present in all three layers of the aorta, whereas PAI-1 immunoreactivity was found in medial smooth muscle cells but not in endothelial cells. After endotoxin treatment, TPA activity was decreased in extracts of the total aorta and of the adventitia, although 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 observations in rat aorta differ from observations in mouse aorta and in rat carotid artery, and they caution against extrapolation from one tissue (or species) to another.