Magnus Giske Snipsøyr1, Henrik Wiggers2, Maja Ludvigsen3, Allan Stensballe4, Henrik Vorum5, Steen Hvitfeldt Poulsen2, Lars Melholt Rasmussen6, Eskild Petersen7, Bent Honoré8. 1. Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aarhus University Hospital, Skejby, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark. 2. Department of Cardiology, Aarhus University Hospital, Skejby, Denmark. 3. Department of Biomedicine, Aarhus University, Aarhus, Denmark. 4. Department of Health Science and Technology, Aalborg University, Denmark. 5. Department of Clinical Medicine, Aalborg University, Denmark. 6. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark. 7. Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark. 8. Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Clinical Medicine, Aalborg University, Denmark. Electronic address: bh@biomed.au.dk.
Abstract
INTRODUCTION: Infective endocarditis (IE) has high mortality, partly due to delayed diagnosis. No biomarker can identify IE in patients with fever and clinical picture of infection. To find putative biomarkers we analyzed serum levels of two proteins found in cardiac valves, fibulin-1 (n=696) and osteoprotegerin (n=689) among patients on clinical suspicion of IE. Proteomic analyses were performed in 24 patients with bacteremia, 12 patients with definite IE and 12 patients with excluded IE. METHODS: Fibulin-1 and osteoprotegerin were studied by enzyme linked immunosorbent assay (ELISA). Proteomic analyses were conducted by 2-dimensional polyacrylamid gel electrophoresis (2D-PAGE) and label-free quantitative liquid chromatography - tandem mass spectrometry (LFQ LC-MS/MS). Controls for 2D 2D-PAGE and LFQ LC-MS/MS had bacteremia and excluded IE. RESULTS: Osteoprotegerin levels were significantly increased in IE patients compared with non-IE patients. Fibulin-1 showed no difference. 2D-PAGE showed significant differences of 6 proteoforms: haptoglobin, haptoglobin-related protein, α-2-macroglobulin, apolipoprotein A-I and ficolin-3. LFQ LC-MS/MS analysis revealed significant level changes of 7 proteins: apolipoprotein L1, complement C1q subcomponent B and C, leukocyte immunoglobulin-like receptor subfamily A member 3, neuropilin-2, multimerin-1 and adiponectin. CONCLUSIONS: The concentration changes in a set of proteoforms/proteins suggest that stress and inflammation responses are perturbed in patients with IE compared to patients with bacteremia without IE.
INTRODUCTION:Infective endocarditis (IE) has high mortality, partly due to delayed diagnosis. No biomarker can identify IE in patients with fever and clinical picture of infection. To find putative biomarkers we analyzed serum levels of two proteins found in cardiac valves, fibulin-1 (n=696) and osteoprotegerin (n=689) among patients on clinical suspicion of IE. Proteomic analyses were performed in 24 patients with bacteremia, 12 patients with definite IE and 12 patients with excluded IE. METHODS:Fibulin-1 and osteoprotegerin were studied by enzyme linked immunosorbent assay (ELISA). Proteomic analyses were conducted by 2-dimensional polyacrylamid gel electrophoresis (2D-PAGE) and label-free quantitative liquid chromatography - tandem mass spectrometry (LFQ LC-MS/MS). Controls for 2D 2D-PAGE and LFQ LC-MS/MS had bacteremia and excluded IE. RESULTS:Osteoprotegerin levels were significantly increased in IEpatients compared with non-IEpatients. Fibulin-1 showed no difference. 2D-PAGE showed significant differences of 6 proteoforms: haptoglobin, haptoglobin-related protein, α-2-macroglobulin, apolipoprotein A-I and ficolin-3. LFQ LC-MS/MS analysis revealed significant level changes of 7 proteins: apolipoprotein L1, complement C1q subcomponent B and C, leukocyte immunoglobulin-like receptor subfamily A member 3, neuropilin-2, multimerin-1 and adiponectin. CONCLUSIONS: The concentration changes in a set of proteoforms/proteins suggest that stress and inflammation responses are perturbed in patients with IE compared to patients with bacteremia without IE.
Authors: Eva Torres-Sangiao; Alexander Dyason Giddey; Cristina Leal Rodriguez; Zhiheng Tang; Xiaoyun Liu; Nelson C Soares Journal: Front Med (Lausanne) Date: 2022-05-02
Authors: Joop J P Kouijzer; Daniëlle J Noordermeer; Wouter J van Leeuwen; Nelianne J Verkaik; Kirby R Lattwein Journal: Front Cell Dev Biol Date: 2022-10-03