Endoluminal arterial injury in plasminogen-deficient mice

Background. Vascular remodeling following arterial injury is characterized by an initial inflammatory reaction, Prior experiments using peritoneal inflammatory models have shown that the plasminogen system plays a role in the intensity of the inflammatory response. This study was undertaken to test the hypothesis that an absence of plasminogen would lead to a decrease in vascular remodeling. Methods. A left carotid artery injury was created with a flexible guidewire in both wild-type [Plg(+/+)] and plasminogen deficient [Plg(-/-)] mice. The right carotid artery was uninjured and used as a control, Three weeks postinjury, the mice were sacrificed and perfusion fixed, and the bilateral carotid arteries were sectioned for histological examination and collection of morphometric data. Results. After arterial injury, electron microscopy of the acutely injured artery revealed that the endothelium was denuded, that there were breaks in the internal elastic membrane, and that there was disruption of the medial layer of smooth muscle cells. The intimal and medial areas were significantly increased between the uninjured and injured carotid arteries of both Plg(+/+) (+80% intimal, +41% medial, P < 0.05) and Plg(-/-) [+48% intimal, +24% medial, P < 0.05) mice. However, although there was a significant increase in the adventitial area of Plg(+/+) mice (+18%, P < 0.05), there was no difference in Plg(-/-) mice (-6%). Interestingly, even after 3 weeks, four of six injured arteries in Plg(-/-) mice had persistent thrombus within the medial layer, whereas this was not found in any of the nine Plg(+/+) mouse arteries. Discussion. Plasminogen deficiency inhibited the increase in adventitial area seen after injury in Plg(+/+) mice, but not the increase in intimal or medial areas, Not surprisingly, plasminogen-deficient mice also demonstrated a severe alteration in intramural thrombus clearance. Thus, specific aspects of the vascular remodeling response are dependent on plasminogen. (C) 2000 Academic Press.