Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease.
Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease.
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DOI：
10.1016/j.jtcvs.2012.12.027
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发表时间：
2013-05
影响因子：
6
通讯作者：
Jones, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Ikonomidis, John S.;Ivey, Charlotte R.;Wheeler, Jason B.;Akerman, Adam W.;Rice, Allison;Patel, Risha K.;Stroud, Robert E.;Shah, Asad A.;Hughes, Chad G.;Ferrari, Giovanni;Mukherjee, Rupak;Jones, Jeffrey A.
胸主动脉瘤（TAA）通过无症状的过程发展，导致大体扩张，如果未被发现和治疗，则进展为破裂。如果检测到，对TAA患者进行一段时间的随访，直到破裂风险超过手术修复风险。目前用于跟踪TAA大小的方法限于昂贵的计算机断层扫描或磁共振成像，因为目前没有可接受的人群筛查工具可用。本实验室和其他实验室的先前研究已经确定了二叶式主动脉瓣（BAV）患者与特发性退行性疾病和三叶式主动脉瓣（TAV）患者的升主动脉瓣组织中基质金属蛋白酶（MMP）及其内源性组织抑制剂（TIMP）的差异蛋白质谱。此外，与正常主动脉组织相比，TAA中的microRNA（miR）表达水平也有所改变。本研究的目的是确定血浆中的循环因子，这些因子可作为区分动脉瘤疾病病因亚型的潜在生物标志物。手术切除时，从BAV（n=21）和TAV（n=21）患者中获得上行TAA组织和血浆标本。使用多分析物蛋白质谱系统或通过定量PCR分别检测关键MMP（-1、-2、-3、-8、-9）和TIMP（-1、-2、-3、-4）以及microRNA（-1、-21、-29 a、-133 a、-143、-145）的蛋白质丰度。将结果与从无主动脉疾病的患者（n=10）获得的正常主动脉组织和血浆进行比较。BAV和TAV主动脉组织样本之间标准化miR-1和miR-21丰度的显著差异（p < 0.05），以及在BAV和TAV组之间观察到的正常主动脉分析物差异的不同组织和血浆谱。线性回归分析仅对于MMP-8和TIMP-1、-3和-4在血浆和组织测量中具有显著的线性关系（p < 0.05）。受试者操作曲线分析揭示了预测TAA疾病的分析物的特异性盒。相对于正常主动脉，MMP-1、-2和7的BAV蛋白水解平衡显著增加，MMP-8和-9降低。相比之下，相对于正常主动脉，TAV蛋白水解平衡仅MMP-1显著增加，MMP-8和MMP-9降低。总之，这些独特的数据证明了来自BAV和TAV患者的上行TAA标本中MMP、TIMP和miR的差异血浆谱。这些结果表明，循环生物标志物可以形成更广泛的生物标志物平台的基础，这些生物标志物能够使用简单的血液检查检测TAA的存在，并且也可以用于个性化的医学策略，以区分动脉瘤疾病患者中TAA的病因亚型。
Thoracic aortic aneurysms (TAAs) develop through an asymptomatic process resulting in gross dilatation that progresses to rupture if left undetected and untreated. If detected, TAA patients are followed over time until the risk of rupture outweighs the risk of surgical repair. Current methodologies for tracking TAA size are limited to expensive computed tomography or magnetic resonance imaging, as no acceptable population screening tools are currently available. Previous studies from this laboratory and others have identified differential protein profiles for the matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs), in ascending TAA tissue from patients with bicuspid aortic valves (BAV), versus patients with idiopathic degenerative disease and a tricuspid aortic valve (TAV). Additionally, altered microRNA (miR) expression levels have also been reported in TAAs as compared to normal aortic tissue. The objective of the present study was to identify circulating factors within the plasma that could serve as potential biomarkers for distinguishing etiological subtypes of aneurysm disease. Ascending TAA tissue and plasma specimens were obtained from BAV (n=21) and TAV (n=21) patients at the time of surgical resection. The protein abundance of key MMPs (-1, -2, -3, -8, -9) and TIMPs (-1, -2, -3, -4), and microRNAs (-1, -21, -29a, -133a, -143, -145) was examined using a multi-analyte protein profiling system or by quantitative PCR, respectively. Results were compared to normal aortic tissue and plasma obtained from patients without aortic disease (n=10). Significant (p < 0.05) differences in standardized miR-1 and miR-21 abundance between BAV and TAV aortic tissue samples and different tissue and plasma profiles of analyte differences from normal aorta where observed between the BAV and TAV groups. Linear regression analysis significant linear relationships in plasma and tissue measurements only for MMP-8 and TIMPs -1, -3 and -4 (p < 0.05). Receiver operator curve analysis revealed specific cassettes of analytes predictive of TAA disease. Relative to normal aorta, BAV proteolytic balance was significantly increased for MMP-1, -2 and -7, and for decreased MMP-8 and -9. In contrast, TAV proteolytic balance relative to normal aorta was significantly increased only for MMP-1 and decreased for MMP-8 and -9. Taken together these unique data demonstrate differential plasma profiles of MMPs, TIMPs, and miRs in ascending TAA specimens from patients with BAV and TAV. These results suggest that circulating biomarkers may form the foundation for a broader platform of biomarkers capable of detecting the presence of TAA using a simple blood test and may also be useful in personalized medicine strategies to distinguish between etiological subtypes of TAAs in patients with aneurysm disease.
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影响因子：
3.2
作者：
Karakaya, O;Barutcu, I;Kaymaz, C
通讯作者：
Kaymaz, C
DOI：
10.1016/j.ejvs.2011.10.014
发表时间：
2012-02-01
影响因子：
5.7
作者：
Hellenthal, F. A. M. V. I.;Ten Bosch, J. A.;Schurink, G. W. H.
通讯作者：
Schurink, G. W. H.
影响因子：
37.8
作者：
Small EM;Frost RJ;Olson EN
通讯作者：
Olson EN
影响因子：
12.3
作者：
Mestdagh P;Van Vlierberghe P;De Weer A;Muth D;Westermann F;Speleman F;Vandesompele J
通讯作者：
Vandesompele J
影响因子：
6
作者：
Essa, Essa M.;Zile, Michael R.;Stroud, Robert E.;Rice, Allison;Gumina, Richard J.;Leier, Carl V.;Spinale, Francis G.
通讯作者：
Spinale, Francis G.