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Inverse changes in plasma tetranectin and titin levels in patients with type 2 diabetes mellitus: a potential predictor of acute myocardial infarction?
Acta Pharmacologica Sinica ( IF 8.2 ) Pub Date : 2018-Jul-01 , DOI: 10.1038/aps.2017.141
Mohd Aizat Abdul Rahim , Zubaidah Haji Abdul Rahim , Wan Azman WAN Ahmad , Marina Mohd Bakri , Muhammad Dzafir Ismail , Onn Haji Hashim

An early intervention using biomarkers to predict acute myocardial infarction (AMI) will effectively reduce global heart attack incidence, particularly among high-risk patients with type 2 diabetes mellitus (T2DM). This study attempted to identify potential biomarkers by detecting changes in the levels of plasma proteins in T2DM patients following onset of AMI in comparison with those without AMI. Volunteer T2DM patients without AMI (control; n=10) and T2DM patients with AMI (n=10) were recruited. Plasma samples from these patients were evaluated via two-dimensional gel electrophoresis (2DE) to screen for proteins with level changes between the two groups. The abundance of spots on gel images was analyzed using Progenesis SameSpots and subjected to false discovery rate (FDR) analysis. Protein spots with statistically significant changes of at least 1.5 fold were selected for mass spectrometry (MS) analysis. Due to strong cardiac connections, tetranectin and titin were evaluated by enzymelinked immunosorbent assay (ELISA). The adjusted P-values and fold changes between the two groups resulted in identification of 34 protein spots with significantly altered abundance. Upon MS analysis, 17 plasma proteins were identified: tetranectin, titin, clusterin, haptoglobin, myosin-13, zinc fnger protein 445, DNA repair protein RAD50, serum albumin, apolipoprotein A-IV, caspase-6, aminoacyl tRNA synthase complex-interacting multifunctional protein 1, serotransferrin, retinol-binding protein 4, transthyretin, alpha-1-antitrypsin, apolipoprotein A-I and serum amyloid A. Comparable patterns of changes in tetranectin and titin between the control and AMI groups were confirmed using ELISA. In summary, tetranectin and titin in plasma appeared to be closely associated with the onset of AMI among T2DM patients and can be used as potential biomarkers for prediction of a cardiac event, though this requires validation in a prospective cohort study.

中文翻译:

2型糖尿病患者血浆四连蛋白和肌酐水平的逆变化:急性心肌梗死的潜在预测指标吗?

早期使用生物标记物进行干预以预测急性心肌梗塞(AMI)可以有效降低整体心脏病发作的发生率,特别是在2型糖尿病(T2DM)高危患者中。这项研究试图通过检测与没有AMI的AMI患者相比,在AMI发作后的T2DM患者中血浆蛋白水平的变化来识别潜在的生物标志物。招募没有AMI的自愿性T2DM患者(对照组; n = 10)和患有AMI的T2DM患者(n = 10)。通过二维凝胶电泳(2DE)对这些患者的血浆样品进行评估,以筛选两组之间水平变化的蛋白质。使用Progenesis SameSpots分析凝胶图像上的大量斑点,并进行假发现率(FDR)分析。选择具有至少1.5倍的统计学显着变化的蛋白质斑点进行质谱分析(MS)。由于强大的心脏连接,因此通过酶联免疫吸附测定(ELISA)评估了四连蛋白和替丁。两组之间调整后的P值和倍数变化导致鉴定出34个蛋白点,其丰度发生了明显变化。经MS分析后,鉴定出17种血浆蛋白:四连蛋白,泰坦,簇蛋白,触珠蛋白,肌球蛋白13,锌指蛋白445,DNA修复蛋白RAD50,血清白蛋白,载脂蛋白A-IV,胱天蛋白酶6,氨酰基tRNA合酶复合物相互作用多功能蛋白1,血清转铁蛋白,视黄醇结合蛋白4,运甲状腺素蛋白,α-1-抗胰蛋白酶,载脂蛋白AI和血清淀粉样蛋白A. 使用ELISA确认了对照组和AMI组之间的​​四连蛋白和肌酐变化的可比模式。总而言之,血浆中的四连蛋白和替丁似乎与T2DM患者中AMI的发作密切相关,可以用作预测心脏事件的潜在生物标志物,尽管这需要在前瞻性队列研究中进行验证。
更新日期:2018-02-08
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