Gasparri Cosimo, Curcio Antonio, Torella Daniele, Gaspari Marco, Celi Vittoria, Salituri Francesco, Boncompagni Duino, Torella Michele, Gulletta Elio, Cuda Giovanni, Indolfi Ciro
Division of Cardiology, Magna Graecia University, Catanzaro, Italy.
Front Biosci (Elite Ed). 2010 Jun 1;2(3):796-804. doi: 10.2741/e140.
The pathogenic mechanisms underlying cardiovascular diseases involve significant alterations in myocardial gene and protein expression. Proteomics analysis can define new protein and peptide changes associated with cardiac pathology, including myocardial infarction. The aim of the present study was to analyze serum proteome of patients with ST-Elevation myocardial infarction (STEMI). Serum samples were collected from STEMI patients (age 65.0+/-10.3) at 5.3+/-2.7 hours after the onset of typical chest pain and before initiating standard therapy. Ten age- and sex-matched donors were used as controls. The samples were albumin- and IgG-depleted. Isotope-coded affinity tag method was employed to label cysteine residues and liquid chromatography-Tandem Mass Spectrometry analysis was performed to measure the labeled proteins. Our proteomic approach identified increased levels of vitamin D-binding protein precursor (VDB) in the serum of STEMI patients when compared to control donors. Western blot analysis confirmed the increase in VDB protein in STEMI patients. Moreover, fresh thrombotic plaques, obtained during primary angioplasty, showed high expression of VDB protein. Mechanistically, VDB protein reduces platelet aggregation and prolongs coagulation time ex vivo.
心血管疾病的发病机制涉及心肌基因和蛋白质表达的显著改变。蛋白质组学分析可以确定与心脏病理学相关的新的蛋白质和肽变化,包括心肌梗死。本研究的目的是分析ST段抬高型心肌梗死(STEMI)患者的血清蛋白质组。在典型胸痛发作后5.3±2.7小时且在开始标准治疗前,从STEMI患者(年龄65.0±10.3)采集血清样本。十名年龄和性别匹配的供体作为对照。样本去除了白蛋白和IgG。采用同位素编码亲和标签法标记半胱氨酸残基,并进行液相色谱-串联质谱分析以测量标记的蛋白质。我们的蛋白质组学方法发现,与对照供体相比,STEMI患者血清中维生素D结合蛋白前体(VDB)水平升高。蛋白质印迹分析证实STEMI患者中VDB蛋白增加。此外,在初次血管成形术中获得的新鲜血栓斑块显示VDB蛋白高表达。从机制上讲,VDB蛋白在体外可减少血小板聚集并延长凝血时间。