A semi-automated mass spectrometric immunoassay coupled to selected reaction monitoring (MSIA-SRM) reveals novel relationships between circulating PCSK9 and metabolic phenotypes in patient cohorts

Methods : a Companion to Methods in Enzymology
Marie-Soleil GauthierBenoit Coulombe

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of circulating low density lipoprotein cholesterol (LDL-C) levels. Besides its full-length mature form, multiple variants of PCSK9 have been reported such as forms that are truncated, mutated and/or with posttranslational modifications (PTMs). Previous studies have demonstrated that most of these variants affect PCSK9's function and thereby LDL-C levels. Commercial ELISA kits are available for quantification of PCSK9, but do not allow discrimination between the various forms and PTMs of the protein. To address this issue and given the complexity and wide dynamic range of the plasma proteome, we have developed a mass spectrometric immunoassay coupled to selected reaction monitoring (MSIA-SRM) for the multiplexed quantification of several forms of circulating PCSK9 in human plasma. Our MSIA-SRM assay quantifies peptides spanning the various protein domains and the S688 phosphorylation site. The assay was applied in two distinct cohorts of obese patients and healthy pregnant women stratified by their circulating LDL-C levels. Seven PCSK9 peptides were monitored in plasma samples: one in the prodomain prior to the autocleavage site at Q152, one in the catalyti...Continue Reading

References

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Citations

Jun 5, 2015·Methods : a Companion to Methods in Enzymology·Benoit Coulombe, Marie-Soleil Gauthier
Nov 14, 2015·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Tove BoströmSophia Hober
Jun 16, 2016·Proteomics·Tujin ShiRichard D Smith
Nov 3, 2016·Diabetes, Obesity & Metabolism·Stéphanie Laugier-RobiolleBertrand Cariou
Aug 22, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Yiming M ZhuSubodh Verma
May 7, 2019·Expert Review of Molecular Diagnostics·Georgia KontostathiAntonia Vlahou
Dec 9, 2016·Analytical and Bioanalytical Chemistry·Rosa PilolliLinda Monaci
Sep 25, 2017·The Journal of Clinical Endocrinology and Metabolism·Marjorie BoyerBenoit J Arsenault
Mar 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sheena WeeJayantha Gunaratne

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