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Mass spectrometric immunoassay and MRM as targeted MS-based quantitative approaches in biomarker development: Potential applications to cardiovascular disease and diabetes

机译:质谱免疫测定和MRM作为生物标志物显影的基于MS的定量方法:潜在应用于心血管疾病和糖尿病

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Type 2 diabetes mellitus (T2DM) is an important risk factor for cardiovascular disease (CVD)the leading cause of death in the United States. Yet not all subjects with T2DM are at equal risk for CVD complications; the challenge lies in identifying those at greatest risk. Therapies directed toward treating conventional risk factors have failed to significantly reduce this residual risk in T2DM patients. Thus newer targets and markers are needed for the development and testing of novel therapies. Herein we review two complementary MS-based approachesmass spectrometric immunoassay (MSIA) and MS/MS as MRMfor the analysis of plasma proteins and PTMs of relevance to T2DM and CVD. Together, these complementary approaches allow for high-throughput monitoring of many PTMs and the absolute quantification of proteins near the low picomolar range. In this review article, we discuss the clinical relevance of the high density lipoprotein (HDL) proteome and Apolipoprotein A-I PTMs to T2DM and CVD as well as provide illustrative MSIA and MRM data on HDL proteins from T2DM patients to provide examples of how these MS approaches can be applied to gain new insight regarding cardiovascular risk factors. Also discussed are the reproducibility, interpretation, and limitations of each technique with an emphasis on their capacities to facilitate the translation of new biomarkers into clinical practice.
机译:2型糖尿病(T2DM)是心血管疾病(CVD)的重要风险因素(CVD)美国死亡原因。然而,并非所有具有T2DM的受试者都具有同等的CVD并发症风险;挑战在于确定最大风险的挑战。针对治疗常规风险因素的疗法未能显着降低T2DM患者的这种残留风险。因此,新的疗法的开发和测试需要更新的目标和标记。在此,我们回顾了两种基于互补的MS基方法,作为MRM的血浆蛋白和与T2DM和CVD相关性的MRM的MRM。这些互补方法在一起允许对许多PTM的高通量监测和低皮质摩拉范围附近的蛋白质的绝对定量。在该综述文章中,我们讨论了高密度脂蛋白(HDL)蛋白质组和载脂蛋白AI PTMS至T2DM和CVD的临床相关性,以及为来自T2DM患者的HDL蛋白质的说明性MSIA和MRM数据提供了这些MS方法的示例可以应用于有关心血管危险因素的新洞察力。还讨论了每种技术的重现性,解释和局限性,重点是促进新生物标志物转化为临床实践的能力。

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