ArticleRapid communications in mass spectrometry : RCM2013
Measurement of apo(a) kinetics in human subjects using a microfluidic device with tandem mass spectrometry.
Article in Rapid communications in mass spectrometry : RCM, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 31 citations in OpenAlex.
- CETP (Cholesteryl Ester Transfer Protein) Inhibition With Anacetrapib Decreases Production of Lipoprotein(a) in Mildly Hypercholesterolemic Subjects.Arteriosclerosis, thrombosis, and vascular biology · 2017Trial
- Apolipoprotein(a) production and clearance are associated with plasma IL-6 and IL-18 levels, dependent on ethnicity.Atherosclerosis · 2024Article
- Cell Analysis on Microfluidics Combined with Mass Spectrometry.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2021Review
- Effects of mipomersen, an apolipoprotein B100 antisense, on lipoprotein (a) metabolism in healthy subjects.Journal of lipid research · 2018Article
- Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study.Journal of lipid research · 2018Article
- Unbiased and targeted mass spectrometry for the HDL proteome.Current opinion in lipidology · 2017Review
- Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans.Circulation · 2017Article
- Multiplexed peptide analysis for kinetic measurements of major human apolipoproteins by LC/MS/MS.Journal of lipid research · 2016Article
- Personalized Proteomics: The Future of Precision Medicine.Proteomes · 2016Article
- Practical immunoaffinity-enrichment LC-MS for measuring protein kinetics of low-abundance proteins.Clinical chemistry · 2014Article
- Static and turnover kinetic measurement of protein biomarkers involved in triglyceride metabolism including apoB48 and apoA5 by LC/MS/MS.Journal of lipid research · 2014Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleApolipoprotein(a) [apo(a)] is the defining protein component of lipoprotein(a) [Lp(a)], an independent risk factor for cardiovascular disease. The regulation of Lp(a) levels in blood is poorly understood in part due to technical challenges in measuring Lp(a) kinetics. Improvements in the ability to readily and reliably measure the kinetics of apo(a) using a stable isotope labeled tracer is expected to facilitate studies of the role of Lp(a) in cardiovascular disease. Since investigators typically determine the isotopic labeling of protein-bound amino acids following acid-catalyzed hydrolysis of a protein of interest [e.g., apo(a)], studies of protein synthesis require extensive protein purification which limits throughput and often requires large sample volumes. We aimed to develop a rapid and efficient method for studying apo(a) kinetics that is suitable for use in studies involving human subjects.
methodsMicrofluidic device and tandem mass spectrometry were used to quantify the incorporation of [(2)H3]-leucine tracer into protein-derived peptides.
resultsWe demonstrated that it is feasible to quantify the incorporation of [(2)H3]-leucine tracer into a proteolytic peptide from the non-kringle repeat region of apo(a) in human subjects. Specific attention was directed toward optimizing the multiple reaction monitoring (MRM) transitions, mass spectrometer settings, and chromatography (i.e., critical parameters that affect the sensitivity and reproducibility of isotopic enrichment measurements). The results demonstrated significant advantages with the use of a microfluidic device technology for studying apo(a) kinetics, including enhanced sensitivity relative to conventional micro-flow chromatography, a virtually drift-free elution profile, and a stable and robust electrospray.
conclusionsThe technological advances described herein enabled the implementation of a novel method for studying the kinetics of apo(a) in human subjects infused with [(2)H3]-leucine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.