Division of Cardiovascular Diseases, Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
JACC Cardiovasc Imaging. 2010 Jan;3(1):32-40. doi: 10.1016/j.jcmg.2009.10.009. Epub 2010 Jan 12.
Our aim was to investigate the role of coronary vasa vasorum (VV) neovascularization in the progression and complications of human coronary atherosclerotic plaques.
Accumulating evidence supports an important role of VV neovascularization in atherogenesis and lesion location determination in coronary artery disease. VV neovascularization can lead to intraplaque hemorrhage, which has been identified as a promoter of plaque progression and complications like plaque rupture. We hypothesized that distinctive patterns of VV neovascularization and associated plaque complications can be found in different stages of human coronary atherosclerosis.
Hearts from 15 patients (age 52+/-5 years, mean+/-SEM) were obtained at autopsy, perfused with Microfil (Flow Tech, Inc., Carver, Massachusetts), and subsequently scanned with micro-computed tomography (CT). The 2-cm segments (n=50) were histologically classified as either normal (n=12), nonstenotic plaque (<50% stenosis, n=18), calcified (n=10) or noncalcified (n=10) stenotic plaque. Micro-CT images were analyzed for VV density (number/mm2), VV vascular area fraction (mm2/mm2), and VV endothelial surface fraction (mm2/mm3). Histological sections were stained for Mallory's (iron), von Kossa (calcium), and glycophorin-A (erythrocyte fragments) as well as endothelial nitric oxide synthase, vascular endothelial growth factor, and tumor necrosis factor-alpha.
VV density was higher in segments with nonstenotic and noncalcified stenotic plaques as compared with normal segments (3.36+/-0.45, 3.72+/-1.03 vs. 1.16+/-0.21, p<0.01). In calcified stenotic plaques, VV spatial density was lowest (0.95+/-0.21, p<0.05 vs. nonstenotic and noncalcified stenotic plaque). The amount of iron and glycophorin A was significantly higher in nonstenotic and stenotic plaques as compared with normal segments, and correlated with VV density (Kendall-Tau correlation coefficient 0.65 and 0.58, respectively, p<0.01). Moreover, relatively high amounts of iron and glycophorin A were found in calcified plaques. Further immunohistochemical characterization of VV revealed positive staining for endothelial nitric oxide synthase and tumor necrosis factor-alpha but not vascular endothelial growth factor.
Our results support a possible role of VV neovascularization, VV rupture, and intraplaque hemorrhage in the progression and complications of human coronary atherosclerosis.
本研究旨在探讨冠状动脉血管新生在人类冠状动脉粥样硬化斑块进展和并发症中的作用。
越来越多的证据支持血管新生在动脉粥样形成和冠状动脉疾病中病变部位确定中的重要作用。血管新生可导致斑块内出血，这已被确定为促进斑块进展和斑块破裂等并发症的因素。我们假设在人类冠状动脉粥样硬化的不同阶段可以发现不同模式的血管新生和相关的斑块并发症。
15 例患者（年龄 52+/-5 岁，平均值+/-SEM）死后取心，用 Microfil（FlowTech，Inc.，马萨诸塞州 Carver）灌注，随后用微计算机断层扫描（CT）扫描。2cm 节段（n=50）经组织学分类为正常（n=12）、非狭窄斑块（<50%狭窄，n=18）、钙化斑块（n=10）或非钙化狭窄斑块（n=10）。对微血管 CT 图像进行血管密度（每毫米的数量）、血管面积分数（每平方毫米的面积）和血管内皮表面积分数（每立方毫米的面积）分析。组织学切片用马洛里（铁）、冯·科萨（钙）和糖蛋白-A（红细胞碎片）以及内皮型一氧化氮合酶、血管内皮生长因子和肿瘤坏死因子-α染色。
与正常节段相比，非狭窄和非钙化狭窄斑块的血管密度更高（3.36+/-0.45、3.72+/-1.03 与 1.16+/-0.21，p<0.01）。在钙化狭窄斑块中，血管空间密度最低（0.95+/-0.21，p<0.05 与非狭窄和非钙化狭窄斑块相比）。与正常节段相比，非狭窄和狭窄斑块中的铁和糖蛋白 A 含量明显更高，与血管密度相关（Kendall-Tau 相关系数分别为 0.65 和 0.58，p<0.01）。此外，在钙化斑块中还发现了相对较高量的铁和糖蛋白 A。进一步的血管新生免疫组织化学特征显示内皮型一氧化氮合酶和肿瘤坏死因子-α阳性染色，但血管内皮生长因子阴性染色。
我们的结果支持血管新生、血管破裂和斑块内出血在人类冠状动脉粥样硬化斑块进展和并发症中的可能作用。
