title: Exploring the human plasma proteome for humoral mediators of remote ischemic preconditioning--a word of caution.
abstract: Despite major advances in early revascularization techniques, cardiovascular diseases are still the leading cause of death worldwide, and myocardial infarctions contribute heavily to this. Over the past decades, it has become apparent that reperfusion of blood to a previously ischemic area of the heart causes damage in and of itself, and that this ischemia reperfusion induced injury can be reduced by up to 50% by mechanical manipulation of the blood flow to the heart. The recent discovery of remote ischemic preconditioning (RIPC) provides a non-invasive approach of inducing this cardioprotection at a distance. Finding its endogenous mediators and their operative mode is an important step toward increasing the ischemic tolerance. The release of humoral factor(s) upon RIPC was recently demonstrated and several candidate proteins were published as possible mediators of the cardioprotection. Before clinical applicability, these potential biomarkers and their efficiency must be validated, a task made challenging by the large heterogeneity in reported data and results. Here, in an attempt to reproduce and provide more experimental data on these mediators, we conducted an unbiased in-depth analysis of the human plasma proteome before and after RIPC. From the 68 protein markers reported in the literature, only 28 could be mapped to manually reviewed (Swiss-Prot) protein sequences. 23 of them were monitored in our untargeted experiment. However, their significant regulation could not be reproducibly estimated. In fact, among the 394 plasma proteins we accurately quantified, no significant regulation could be confidently and reproducibly assessed. This indicates that it is difficult to both monitor and reproduce published data from experiments exploring for RIPC induced plasma proteomic regulations, and suggests that further work should be directed towards small humoral factors. To simplify this task, we made our proteomic dataset available via ProteomeXchange, where scientists can mine for novel potential targets.
authors.affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Helgeland
authors.affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Lars Ertesvåg
authors.initials: LE
authors.lastname: Breivik
authors.affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Marc
authors.initials: M
authors.lastname: Vaudel
authors.affiliation: Department of Anaesthesia and Surgical Services, Haukeland University Hospital, Bergen, Norway.
authors.forename: Øyvind Sverre
authors.initials: ØS
authors.lastname: Svendsen
authors.affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Hilde
authors.initials: H
authors.lastname: Garberg
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Nordrehaug
authors.affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Frode Steingrimsen
authors.initials: FS
authors.lastname: Berven
authors.affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
authors.forename: Anne Kristine
authors.initials: AK
authors.lastname: Jonassen
mesh_terms: D030562:Databases, Protein; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics
chemical_list: D020543:Proteome