Abstract 3655: The Anti−Angiogenic Activity of rPAI-123 Inhibits Vasa Vasorum and Growth of Atherosclerotic Plaque
Plaque vascularity has been implicated in its growth and stability. However, there is a paucity of information regarding the origin of plaque vasculature and the role of vasa vasorum in plaque growth. In this study we used a truncated PAI-1 protein, rPAI-123, that has significant anti-angiogenic activity, to inhibit growth of vasa vasorum in atherogenic mice and assessed its effect on plaque growth. Female LDLR−/−/ApoB-100 mice were fed Paigen’s diet without cholate for 20 weeks while receiving rPAI-1 23 treatment (n= 21) for the last six weeks. Plaque size and vasa vasorum density were compared to two controls, mice fed Paigen’s diet and treated with saline for the last six weeks (n=16) and mice fed Paigen’s diet until the onset of treatment (n=14). The rPAI-123 treatment significantly reduced plaque area by 73% in the descending aorta and 64% in the innominate artery without meaningful reduction in serum cholesterol levels. Measurements of reconstructed confocal microscopy images of vasa vasorum demonstrate that rPAI-123 treatment decreased vasa vasorum area by 37% and length by 43%, which was further supported by microCT images of the vasa vasorum. Confocal images provide evidence for vascularized plaque in the saline treated group, but not in rPAI-123 treated mice. This study demonstrates for the first time that increased vasa vasorum density corresponds with adjacent vessels in significantly larger plaques that are accompanied by vessels in the descending aorta wall, which is not found in mice treated with the angiogenesis inhibitor. In conclusion, rPAI-123 inhibits growth of vasa vasorum as well as vessels within the adjacent plaque and vessel wall, leading to reduced plaque growth in atherogenic female LDLR−/−/ApoB-100 mice.