Plasminogen activators and matrix metalloproteinases during arterial remodeling

To evaluate the role and interaction of plasminogen activators and matrixmetalloproteinases (MMPs) in arterial remodeling in vivo we compared effects of recombinant urokinase- (uPA) and tissue-type (tPA) plasminogen activators on vessel morphology, cell proliferation, inflammatory reaction and MMPs expression in arterial wall after experimental balloon angioplasty. We observed that the periadventitial application of uPA to the injured artery in pluronic gel stimulated neointima formation and inward arterial remodeling as well as cell proliferation and inflammatory leukocytes recruitment. In contrast, tPA attenuated neointima growth, contributed to outward arterial remodeling and did not affect significantly leukocytes recruitment in injured arterial wall. Perivascular uPA increased the content and activity of MMI's, while tPA did not induce such changes. In mouse model of vascular remodeling based on partial ligation of the carotid the content of uPA correlated with neointima growth, tPA content correlated with outward arterial remodeling. Our experiments suggest that plasminogen activators represent specific functional target for attenuating unfavorable inward arterial remodeling.