Endoluminal arterial injury in plasminogen-deficient mice

Background. Vascular remodeling following arterial injury is characterized by an initial inflammatory reaction, Prior experiments using peritoneal inf lammatory 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 v ascular remodeling. Methods. A left carotid artery injury was created with a flexible guidewire in both wild-type [Plg(+/+)] and plasminogen deficient [Plg(-/-)] mice. Th e right carotid artery was uninjured and used as a control, Three weeks pos tinjury, the mice were sacrificed and perfusion fixed, and the bilateral ca rotid arteries were sectioned for histological examination and collection o f 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 significan tly increased between the uninjured and injured carotid arteries of both Pl g(+/+) (+80% intimal, +41% medial, P < 0.05) and Plg(-/-) [+48% intimal, +2 4% medial, P < 0.05) mice. However, although there was a significant increa se 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 ar ea seen after injury in Plg(+/+) mice, but not the increase in intimal or m edial areas, Not surprisingly, plasminogen-deficient mice also demonstrated a severe alteration in intramural thrombus clearance. Thus, specific aspec ts of the vascular remodeling response are dependent on plasminogen. (C) 20 00 Academic Press.