Department of Pharmaceutical Biology, Faculty of Pharmacy &Biotechnology, The German University in Cairo, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Sci Rep. 2016 Nov 8;6:36359. doi: 10.1038/srep36359.
Discovery of novel biomarkers is critical for early diagnosis of acute coronary syndrome (ACS). Serum metabolite profiling of ST-elevation myocardial infarction (STEMI), unstable angina (UA) and healthy controls was performed using gas chromatography mass spectrometry (GC/MS), solid-phase microextraction coupled to gas chromatography mass spectrometry (SPME-GC/MS) and nuclear magnetic resonance (H-NMR). Multivariate data analysis revealed a metabolic signature that could robustly discriminate STEMI patients from both healthy controls and UA patients. This panel of biomarkers consisted of 19 metabolites identified in the serum of STEMI patients. One of the most intriguing biomarkers among these metabolites is hydrogen sulfide (HS), an endogenous gasotransmitter with profound effect on the heart. Serum HS absolute levels were further investigated using a quantitative double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). This highly sensitive immunoassay confirmed the elevation of serum HS in STEMI patients. HS level discriminated between UA and STEMI groups, providing an initial insight into serum-free HS bioavailability during ACS. In conclusion, the current study provides a detailed map illustrating the most predominant altered metabolic pathways and the biochemical linkages among the biomarker metabolites identified in STEMI patients. Metabolomics analysis may yield novel predictive biomarkers that will potentially allow for an earlier medical intervention.
发现新的生物标志物对于急性冠状动脉综合征(ACS)的早期诊断至关重要。采用气相色谱质谱联用(GC/MS)、固相微萃取与气相色谱质谱联用(SPME-GC/MS)和核磁共振(H-NMR)对 ST 段抬高型心肌梗死(STEMI)、不稳定型心绞痛(UA)和健康对照组的血清代谢物谱进行了分析。多变量数据分析显示了一种代谢特征,可以可靠地区分 STEMI 患者与健康对照组和 UA 患者。该生物标志物面板由在 STEMI 患者血清中鉴定出的 19 种代谢物组成。这些代谢物中最有趣的生物标志物之一是硫化氢(HS),一种对心脏有深远影响的内源性气体递质。使用定量双抗体夹心酶联免疫吸附试验(ELISA)进一步研究了血清 HS 的绝对水平。这种高灵敏度的免疫测定法证实了 STEMI 患者血清 HS 的升高。HS 水平区分了 UA 和 STEMI 组,初步了解了 ACS 期间血清游离 HS 的生物利用度。总之,本研究提供了一个详细的图谱,说明了 STEMI 患者中最主要的改变代谢途径和生物标志物代谢物之间的生化联系。代谢组学分析可能会产生新的预测生物标志物,从而有可能更早地进行医学干预。