Expression of Vasohibin-1 in Human Carotid Atherosclerotic Plaque
Expression of Vasohibin-1 in Human Carotid Atherosclerotic Plaque
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DOI：
10.5551/jat.29074
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发表时间：
2015-01-01
影响因子：
4.4
通讯作者：
Miyamoto, Susumu
中科院分区：
文献类型：
--
作者：
Fukumitsu, Ryu;Minami, Manabu;Miyamoto, Susumu
目的：在颈动脉斑块患者中，新生内膜内新生血管破裂引起的斑块内出血是卒中的重要原因。血管生成素-1(Vasohibin-1，VASH1)是血管生成的负反馈调节因子，存在于多种实体瘤的微血管内皮细胞和动脉壁中。然而，VASH1在动脉粥样硬化性疾病发病机制中的作用尚不清楚。本研究旨在阐明VASH1在人颈动脉斑块中的表达与斑块不稳定性的相关性。方法：采用实时定量聚合酶链式反应和免疫组织化学方法检测12例颈动脉内膜切除术后的动脉粥样斑块标本。结果：与对照组相比，动脉粥样硬化斑块中VASH1mRNA的表达显著增加(p=0.018)。此外，VASH1mRNA水平与VEGFA、CD31、VCAM1mRNA水平呈正相关(r=0.788，p=0.004；r=0.99，p=0.001；r=0.94p<；0.001)。免疫组织化学分析显示，VASH1在颈动脉斑块新生内膜微血管内皮细胞中有表达。结论：动脉粥样硬化中VASH1的表达水平既反映了新生血管的增强，又反映了炎症负担。因此，VASH1水平可能成为评价颈动脉硬化患者斑块不稳定性和预测缺血性卒中的一种新的生物标志物。
Aim: In patients with carotid plaque, intraplaque hemorrhage arising from ruptured neovascular vessels within the neointima is an important cause of stroke. The expression of Vasohibin-1 (VASH1), a negative feedback regulator of angiogenesis, occurs in the microvessel endothelial cells of various solid tumors and the arterial wall. However, the roles of VASH1 in the pathogenesis of atherosclerotic diseases remain unclear. The present study aimed to clarify the relevance of the VASH1 expression and plaque instability in human carotid plaques.Methods: We used quantitative real-time PCR and immunostaining to examine 12 atheromatous plaque specimens obtained via carotid endarterectomy. The distal areas of specimens lacking macroscopic atherosclerotic lesions served as controls.Results: Compared with that observed in the controls, the VASH1 gene expression increased significantly in the atheromatous plaque (p=0.018). Moreover, the VASH1 mRNA levels correlated positively with those of VEGFA, CD31 and VCAM1 (r = 0.788, p = 0.004; r = 0.99, p < 0.001; r = 0.94, p< 0.001, respectively). Finally, the immunohistochemical analyses revealed the VASH1 expression in the neointimal microvessel endothelial cells of carotid plaque.Conclusions: The VASH1 expression levels in atheroma reflect both enhanced neovascularization and the inflammatory burden. Therefore, the VASH1 level may be a novel biomarker for evaluating plaque instability in patients with carotid arteriosclerosis and predicting ischemic stroke.