Fukumitsu Ryu, Minami Manabu, Yoshida Kazumichi, Nagata Manabu, Yasui Mika, Higuchi Sei, Fujikawa Risako, Ikedo Taichi, Yamagata Sen, Sato Yasufumi, Arai Hidenori, Yokode Masayuki, Miyamoto Susumu
Department of Neurosurgery, Kyoto University Graduate School of Medicine.
J Atheroscler Thromb. 2015;22(9):942-8. doi: 10.5551/jat.29074. Epub 2015 Apr 3.
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.
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.
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.
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.
在颈动脉斑块患者中，新生内膜内破裂的新生血管引起的斑块内出血是中风的重要原因。血管抑制素-1（VASH1）作为血管生成的负反馈调节因子，在各种实体瘤的微血管内皮细胞和动脉壁中表达。然而，VASH1在动脉粥样硬化疾病发病机制中的作用仍不清楚。本研究旨在阐明VASH1表达与人类颈动脉斑块不稳定性之间的相关性。
我们使用定量实时PCR和免疫染色来检测通过颈动脉内膜切除术获得的12个动脉粥样硬化斑块标本。缺乏宏观动脉粥样硬化病变的标本远端区域作为对照。
与对照组相比，动脉粥样硬化斑块中VASH1基因表达显著增加（p = 0.018）。此外，VASH1 mRNA水平与VEGFA、CD31和VCAM1的水平呈正相关（r分别为0.788，p = 0.004；r = 0.99，p ＜ 0.001；r = 0.94，p ＜ 0.001）。最后，免疫组织化学分析显示颈动脉斑块新生内膜微血管内皮细胞中有VASH1表达。
动脉粥样硬化中VASH1的表达水平反映了新生血管形成的增强和炎症负担。因此，VASH1水平可能是评估颈动脉粥样硬化患者斑块不稳定性和预测缺血性中风的一种新型生物标志物。
