Background:Accumulating evidence indicates a potential role of adventitial vasa vasorum (VV) dysfunction in the pathophysiology of restenosis.However,characterization ofVV vascularization in restenotic arteries with primary lesions is still missing.In this study,we quantitatively evaluated the response of adventitial VV to vascular injury resulting from balloon angioplasty in diseased arteries.Methods:Primary atherosclerotic-like lesions were induced by the placement of an absorbable thread surrounding the carotid artery of New Zealand rabbits.Four weeks following double-injury induced that was induced by secondary balloon dilation,three-dimensional patts of adventitial VV were reconstructed;the number,density,and endothelial surface of VV were quantified using micro-computed tomography.Histology and immunohistochemistry were performed in order to examine the development of intimal hyperplasia.Results:Results from our study suggest that double injured arteries have a greater number of VV,increased luminal surface,and an elevation in the intima/media ratio (I/M),along with an accumulation ofmacrophages and smooth muscle cells in the intima,as compared to sham or single injury arteries.I/M and the number of VV were positively correlated (R2 =0.82,P ＜ 0.001).Conclusions:Extensive adventitial VV neovascularization occurs in injured arteries after balloon angioplasty,which is associated with intimal hyperplasia.Quantitative assessment of adventitial VV response may provide insight into the basic biological process of postangioplasty restenosis.