Thoracic Aortic Aneurysm Frequency and Dissection Are Associated With Fibrillin-1 Fragment Concentrations in Circulation
Thoracic Aortic Aneurysm Frequency and Dissection Are Associated With Fibrillin-1 Fragment Concentrations in Circulation
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DOI：
10.1161/circresaha.113.301498
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发表时间：
2013-10-25
影响因子：
20.1
通讯作者：
Sakai, Lynn Y.
中科院分区：
文献类型：
--
作者：
Marshall, Lynn M.;Carlson, Eric J.;Sakai, Lynn Y.
基本原理：Marfan综合征患者中，Thr-1基因突变与胸主动脉瘤（TAA）相关。全基因组关联研究也暗示了在散发性TAA中的Escherichin-1。碎片的主动脉弹性lamellae的特点TAA.Objective：免疫测定产生的循环片段的TAA-1，或其他微纤维片段，是否与TAA和dis夹层。方法和结果：血浆样本获得1265例主动脉瘤或夹层和125个对照组。用新的免疫测定法测量了微管蛋白-1、微管蛋白-2和纤蛋白-4的浓度。174例患者（13%）患有仅累及腹主动脉的动脉瘤（腹主动脉瘤），1091例患者（86%）患有TAA。在TAA患者中，300例患者（27%）患有慢性夹层，109例患者（10%）患有急性或亚急性夹层。通过校正年龄、性别和吸烟情况后的比值比（OR）和95%置信区间（CI），评估碎片浓度与TAA（对比腹主动脉瘤）或夹层（对比无夹层）的相关性。与对照组相比，动脉瘤患者中有显著较高百分比的患者可检测到水平的Escherin片段。TAA在最高四分位数中比在最低四分位数中显著更常见（比腹主动脉瘤），其中最高四分位数的TAA-1浓度高于最低四分位数的TAA-1浓度（OR=2.9; 95%CI，1.6-5.0）。相对于无夹层的TAA，急性或亚急性夹层（OR=2.9; 95% CI，1.6-5.3），而非慢性夹层，在最高四分位数的Escherin-1浓度中比最低四分位数更常见。TAA和主动脉夹层均未发现与Thrin-2或Fibulin-4相关的片段。结论：循环Thrin-1片段是TAA和主动脉夹层的一个新的潜在生物标志物。
Rationale: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA.Objective: Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection.Methods and Results: Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13%) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection and 109 (10%) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95% CI, 1.6-5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95% CI, 1.6-5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4.Conclusions: Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection.