THE ANTI‐ANGIOGENIC ACTIVITY OF rPAI‐1 23 INHIBITS ANGIOGENIC VASA VASORUM AND ATHERSCLEROTIC PLAQUE GROWTH

Abstract

Introduction: Neovascularized areas in atherosclerosis are primarily supplied by angiogenic vasa vasorum. The vasa vasorum density increases during plaque progression, but the role of angiogenesis in plaque growth is uncertain. A truncated PAI-1 protein, rPAI-123, has significant anti-angiogenic activity. We hypothesized that rPAI-123 inhibition of angiogenic vasa vasorum in atherogenic mice would reduce plaque progression. Methods: Female LDLR−/−/ApoB-100 mice were fed a high fat diet (HFD) for 14 weeks prior to initiating 6 weeks of rPAI-123 (n= 16) or saline (n=11) treatment with continued HFD. Control animals received chow diet and saline treatment. Lipid content, vasa vasorum density, vessel circumference, plaque and lumen areas were measured. Results: rPAI-123 reduced lipid area by 60% and 30% (p<0.001) in the descending aorta and aortic root, respectively as compared to HFD saline treatment. Measurements of reconstructed vessels in the plaque area show that rPAI-123 decreased vessel area and length by 43 and 37% (p = 0.01), respectively. Carotid artery circumferences in rPAI-123 and saline HFD groups were similar. However, rPAI-123 decreased plaque area by 67% (p<0.001) and increased lumen area by 74% (p<0.001). Conclusions: rPAI-123 inhibits angiogenic vasa vasorum, reduces plaque growth and promotes plaque regression in atherogenic female LDLR−/−/ApoB-100 mice.