The present invention provides the use of recombinant plasminogen activator inhibitor-1 (PAI-1) isoform 23 in methods of increasing plasmin activity, inhibiting angiogenic vasa vasorum, promoting plaque regression and treating atherosclerosis by administering to a subject in need of treatment an effective amount of recombinant plasminogen activator inhibitor type isoform 23 (rPAI-123). In some embodiments, rPAI-123 is set forth in SEQ ID NOs:5-8. In other embodiments, rPAI-123 is administered at a dose in the range of approximately 2.5 μg/kg/day to 20 μg/kg/day. In further embodiments, the effective amount achieves a ratio of rPAI-123 to PAI-1 is in the range of approximately 1:2 to 3:1.