Hypoxia accelerates intraplaque neovascularization derived from endothelial progenitor cells in carotid stenosis
Hypoxia accelerates intraplaque neovascularization derived from endothelial progenitor cells in carotid stenosis
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DOI：
10.3171/2018.4.jns172876
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发表时间：
2019-09-01
影响因子：
4.1
通讯作者：
Kuroda, Satoshi
中科院分区：
文献类型：
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作者：
Kashiwazaki, Daina;Koh, Masaki;Kuroda, Satoshi
目的斑块内缺氧与斑块内出血(IPH)的关系已有报道，但具体细节尚不清楚。在这项研究中，作者旨在阐明斑块内缺氧、内皮祖细胞(EPC)和导致IPH的新生血管之间的关系。方法对49例颈动脉内膜切除术患者的颈动脉内膜切除术标本进行组织学分析。用磁共振斑块成像分析颈动脉斑块的成分，并对手术标本进行免疫组织化学分析。结果颈动脉斑块中低氧诱导因子-1α(HIF-1α)、CD34-、CD133和血管内皮生长因子受体-2(VEGFR-2)阳性细胞数、CD31阳性微血管数和最大管径分别为7例、22例和20例。作为EPC特异性标志物的CD34、VEGFR-2和CD133阳性细胞数与HIF-1U阳性细胞数呈显著正相关(r=0.9，r=0.82，r=0.82，P<0.05)。和r=0.81)。这些数字在3种斑块成分(IPH和GT；富脂>；纤维斑块)中有所不同。数量和最大卢米纳！CD31阳性微血管直径与HIF-1α阳性细胞数呈显著正相关(r=0.85和r=0.89)，并随斑块成分(IPH>；富脂纤维)的不同而不同。结论斑块内缺氧可促进内皮祖细胞来源的异常微血管形成，进而促进IPH。结果还表明，微血管扩张是IPH的一个重要特征，这些增大的微血管是未成熟的内皮管，分支紊乱，易碎，容易破裂。
OBJECTIVE The relationship between intraplaque hypoxia and intraplaque hemorrhage (IPH) has been reported, but the details remain obscure. In this study, the authors aimed to clarify the relationship among intraplaque hypoxia, endothelial progenitor cells (EPCs), and neovascularization, which causes IPH. The histological findings of specimens obtained from carotid endarterectomy were assessed.METHODS This study included 49 patients who underwent carotid endarterectomy. Magnetic resonance plaque imaging was performed to analyze the components of the carotid plaques, and surgical specimens were subjected to immunohistochemical analysis. The numbers of hypoxia-inducible factor-1 alpha (HIF-1 alpha)-, CD34-, CD133-, and vascular endothelial growth factor receptor-2 (VEGFR-2)-positive cells in the carotid plaques were precisely quantified, as were the number and maximum diameter of CD31-positive microvessels.RESULTS Plaque components were judged as fibrous in 7 samples, lipid-rich in 22, and IPH in 20. The number of CD34-, VEGFR-2-, and CD133-positive cells as an EPC-specific marker was significantly correlated with the number of HIF-1u-positive cells (r = 0.9, r = 0.82, and r = 0.81, respectively). These numbers varied among the 3 plaque components (IPH > lipid-rich > fibrous). The number and maximum lumina! diameter of CD31-positive microvessels were also significantly correlated with the number of HIF-1 alpha-positive cells (r = 0.85 and r = 0.89, respectively) and varied among the 3 plaque components (IPH > lipid-rich > fibrous).CONCLUSIONS The present findings suggest that intraplaque hypoxia may accelerate abnormal microvessel formation derived from EPCs, which in turn promotes IPH. The results also suggest that microvessel enlargement is a pivotal characteristic of IPH and these enlarged microvessels are immature endothelial tubes with disorganized branching and are fragile and prone to rupture.