Objectives: The objective of this study was to examine the quantitative response of the adventitial vasa vasorum to balloon-induced coronary injury.
Background: Recent attention has focused on the role of vasa vasorum in atherosclerotic and restenotic coronary artery disease. However, the three-dimensional anatomy of these complex vessels is largely unknown, especially after angioplasty injury. The purpose of this study was to visualize and quantitate three-dimensional spatial patterns of vasa vasorum in normal and balloon injured porcine coronary arteries. We also studied the spatial growth of vasa vasorum in regions of neointimal formation. A novel imaging technique, microscopic computed tomography, was used for these studies.
Methods: Four pigs were killed 28 d after coronary balloon injury, and four pigs with uninjured coronary arteries served as normal controls. The coronary arteries were injected with a low-viscosity, radiopaque liquid polymer compound. Normal and injured coronary segments were scanned using a microscopic computed tomography technique. Three-dimensional reconstructed maximum intensity projection and voxel gradient shading images were displayed at different angles and voxel threshold values, using image analysis software. For quantitation, seven to 10 cross-sectional images (40 normal and 32 balloon injured cross-sections) were captured from each specimen at a voxel size of 21 microm.
Results: Normal vasa vasorum originated from the coronary artery lumen, principally at large branch points. Two different types of vasa were found and classified as first-order or second-order according to location and direction. In balloon-injured coronary arteries, adventitial vasa vasorum density was increased (3.16+/-0.17/mm2 vs. 1.90+/-0.06/mm2, p = 0.0001; respectively), suggesting neovascularization by 28 d after vessel injury. Also, in these injured arteries, the vasa spatial distribution was disrupted compared with normal vessels, with proportionally more second-order vasa vasorum. The diameters of first-order and second-order vasa were smaller in normal compared with balloon-treated coronary arteries (p = 0.012 first-order; p < 0.001, second-order; respectively). The density of newly formed vasa vasorum was proportional to vessel stenosis (r = 0.81, p = 0.0001). Although the total number of vasa was increased after injury, the total vascular area comprised of vasa was significantly reduced in injured vessels compared with normals (3.83+/-0.20% to 5.42+/-0.56%, p = 0.0185).
Conclusions: Adventitial neovascularization occurs after balloon injury. The number of new vessels is proportional to vessel stenosis. These findings may hold substantial implications for the therapy of vascular disease and restenosis.