Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea.
Translational and Stem Cell Research Laboratory on Stroke Samsung Medical Center Seoul Korea.
J Am Heart Assoc. 2019 Oct 15;8(20):e011996. doi: 10.1161/JAHA.119.011996. Epub 2019 Oct 8.
Background Intracranial atherosclerotic stroke is prevalent in Asians. We hypothesized that patients with the ring finger protein 213 () variant, a susceptibility locus for moyamoya disease in Asians, have different neuroimaging characteristics in terms of the vessel wall and hemodynamics. Methods and Results We analyzed consecutive patients with ischemic events in middle cerebral artery distribution and relevant plaques of the distal internal carotid artery or proximal middle cerebral artery on high-resolution magnetic resonance imaging. Patients with carotid/cardiac sources of embolism or moyamoya disease were excluded. High-resolution magnetic resonance imaging features (eg, outer vessel diameters and plaque characteristics) and fractional flow (as measured by adjusted signal intensity ratio on time-of-flight magnetic resonance angiography) were compared between p.Arg4810Lys variant carriers and noncarriers. Among 144 patients included, 44 (29.9%) had the variant. Clinical characteristics, including age, sex, body mass index, and vascular risk factors, were not significantly different between variant carriers and noncarriers. However, the outer vessel diameter was smaller in variant carriers than in noncarriers (<0.0001 for middle cerebral artery of relevant stenosis [2.05-mm analysis of RNF213 gene for moyamoya disease in the Chinese HAN population 2.75 mm]; <0.0001 for contralateral side [2.42 versus 3.00 mm] and <0.001 for basilar artery [3.19 versus 3.53 mm]). Other high-resolution magnetic resonance imaging features, including plaque morphology and eccentricity, were not significantly different. Fractional flow was diminished in patients with smaller-diameter intracranial arteries with a similar degree of stenosis. Conclusions The variant may be associated with vasculogenesis, but not with atherogenesis. Patients with this variant had small intracranial arteries predisposing hemodynamic compromise in the presence of intracranial atherosclerosis. In addition to antiatherosclerotic strategies, further studies are warranted to develop novel therapeutic strategies against vasculopathy in Asians.
颅内动脉粥样硬化性卒中在亚洲人群中较为常见。我们推测,携带亚洲人易患烟雾病的环指蛋白 213 (RNF213)变异的患者,其血管壁和血流动力学方面的神经影像学特征可能不同。
我们分析了连续的大脑中动脉分布区缺血事件患者,以及远端颈内动脉或近端大脑中动脉相关斑块的高分辨率磁共振成像。排除了有颈动脉/心源性栓塞来源或烟雾病的患者。比较了 RNF213 基因 p.Arg4810Lys 变异携带者和非携带者的高分辨率磁共振成像特征(如外血管直径和斑块特征)和分数流(通过调整时间飞越磁共振血管造影的信号强度比测量)。在纳入的 144 例患者中,有 44 例(29.9%)携带该变异。变异携带者和非携带者的临床特征,包括年龄、性别、体重指数和血管危险因素,无显著差异。然而,变异携带者的外血管直径小于非携带者(相关狭窄的大脑中动脉[2.05mm 分析]为 2.75mm;对侧为[2.42mm 对 3.00mm],基底动脉为[3.19mm 对 3.53mm],均<0.0001)。其他高分辨率磁共振成像特征,包括斑块形态和偏心度,无显著差异。在狭窄程度相似的情况下,较小直径颅内动脉的患者分数流减少。
RNF213 变异可能与血管生成有关,而与动脉粥样硬化形成无关。携带该变异的患者颅内动脉较小,在存在颅内动脉粥样硬化的情况下易发生血流动力学紊乱。除了抗动脉粥样硬化策略外,还需要进一步研究,以制定针对亚洲人 RNF213 血管病的新治疗策略。