Donor PAI-1 expression inhibits the intimal response of early allograft vascular disease

The development of allograft vascular disease (AVD) may be related to altered expression of the fibrinolytic system. We determined the extent to which plasminogen activator inhibitor type 1 (PAI-1) expression in donor tissue influences intimal proliferation (IP) in a mouse model of AVD.

We utilized an end-to-end abdominal aortic transplant model in mice to investigate the development of IP in 3 groups of 6 recipients. Group A (negative control) utilized C57BL/6J strain mice as both donors and recipients. In Groups B (positive control) and C, C57BL/6J mice were vessel donors and CBA/J mice were recipients. Both groups received intraperitoneal anti-CD4 and anti-CD8 monoclonal antibodies (250 microg/week for 5 weeks). Group C recipients, however, were transplanted with vessels from C57BL/6J PAI-1 knockout mice. Animals were killed at 50 days. Transplanted aortas were removed and intimal areas calculated using morphometric analysis.

Group A (mean intimal area 6421 +/- 8507 microm(2)) demonstrated very little IP in comparison to the other groups. IP was significantly higher in Group B (mean intimal area 56357 +/- 35629 microm(2)) than Group A (p = 0.008). Group C (mean intimal area 288195 +/- 123279 microm(2)) demonstrated significantly more intimal proliferation than either Groups A or B (vs B, p = 0.003; vs A, p < 0.001). The significance of these results is maintained if intimal thickness is measured as a stand-alone reference for the intimal response.

Lack of PAI-1 expression in donor tissue greatly exaggerates the extent of IP after allogeneic transplantation and suggests that PAI-1 is important in limiting the early phase of AVD.