Naz Shama, Calderón Ángela Algaba, García Antonia, Gallafrio Jessica, Mestre Rodrigo Teijeiro, González Elena González, de Cabo Carlos Muñoz, Delgado Mari Cruz Martín, Balanza José Ángel Lorente, Simionato Ana Valéria Colnaghi, Vaeza Nicolás Nin, Barbas Coral, Rupérez Francisco J
CEMBIO, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
Hospital Universitario de Torrejón, Madrid, Spain.
Electrophoresis. 2015 Sep;36(18):2303-2313. doi: 10.1002/elps.201500169. Epub 2015 Aug 27.
Differences in the degree and severity of Acute Coronary Syndrome, associated to differences in the electrocardiogram, together with blood tests of biomarkers classify patients for diagnosis and treatment. Cases where the electrocardiogram and/or biomarkers are not conclusive still appear, and there is a need for complementary biomarkers for routine determinations. Metabolomics approaches with blind fingerprinting could reveal differences in metabolites, which must be confirmed by means of targeted determinations. CE-MS and HILIC-MS are well suited for the determination of highly polar compounds, like those from to the intermediate metabolism, altered due to acute stress induced by myocardial infarction. Serum from patients with ST-elevated and non-ST elevated myocardial infarction was collected at intensive care and emergency units, and fingerprinted with CE-MS. Data pretreatment and analysis showed up carnitine-related compounds and amino acids differentially present in both groups. Acylcarnitines and amino acids were then quantitatively measured with HILIC-MS-QqQ. The significance of the differences and the sensitivity/specificity of each compound were individually evaluated. The ratio of free carnitine to acylcarnitines, together with the ratios of acetylcarnitine to betaine, to threonine, and to citrulline, showed high significance and area under the curve in the respective receiver operating characteristic curves. This study opens new possibilities for defining new sets of biomarkers for refining the diagnosis of the patients with difficult classification.
急性冠状动脉综合征在程度和严重性上的差异,与心电图差异以及生物标志物血液检测结果相关联,这些因素共同用于对患者进行诊断和治疗分类。然而,心电图和/或生物标志物不确定的情况仍然存在,因此需要补充生物标志物用于常规检测。采用盲法指纹识别的代谢组学方法可以揭示代谢物的差异,这些差异必须通过靶向检测来确认。毛细管电泳-质谱联用(CE-MS)和亲水作用色谱-质谱联用(HILIC-MS)非常适合测定高极性化合物,例如那些因心肌梗死引起的急性应激而改变的中间代谢产物。在重症监护病房和急诊科收集了ST段抬高型心肌梗死和非ST段抬高型心肌梗死患者的血清,并采用CE-MS进行指纹识别。数据预处理和分析显示,两组中肉碱相关化合物和氨基酸的存在情况存在差异。然后用HILIC-MS-QqQ对酰基肉碱和氨基酸进行定量测定。分别评估了各化合物差异的显著性以及敏感性/特异性。游离肉碱与酰基肉碱的比值,以及乙酰肉碱与甜菜碱、苏氨酸和瓜氨酸的比值,在各自的受试者工作特征曲线中显示出高度显著性和曲线下面积。这项研究为定义新的生物标志物集以完善难以分类患者的诊断开辟了新的可能性。