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Proteomic Profiling in Patients With Peripartum Cardiomyopathy

医学 围产期心肌病 内科学 发病机制 利钠肽 心肌病 生物信息学 心力衰竭 生物
作者
Vitaris Kodogo,Charle Viljoen,Julian Hoevelmann,Graham Chakafana,Jasper Tromp,Hasan Ali Farhan,Sorel Goland,Peter van der Meer,Kamilu M Karaye,Karolina Kryczka,Denise Hilfiker‐Kleiner,Alice M Jackson,Alexandre Mebazaa,Michael Böhm,Burkert Pieske,Johann Bauersachs,Liam Bell,Karen Sliwa
出处
期刊:Jacc-Heart Failure [Elsevier]
卷期号:11 (12): 1708-1725 被引量:2
标识
DOI:10.1016/j.jchf.2023.07.028
摘要

Peripartum cardiomyopathy (PPCM) remains an important cause of maternal morbidity and mortality globally. The pathophysiology remains incompletely understood, and the diagnosis is often missed or delayed.This study explored the serum proteome profile of patients with newly diagnosed PPCM, as compared with matched healthy postpartum mothers, to unravel novel protein biomarkers that would further an understanding of the pathogenesis of PPCM and improve diagnostic precision.Study investigators performed untargeted serum proteome profiling using data-independent acquisition-based label-free quantitative liquid chromatography-tandem mass spectrometry on 84 patients with PPCM, as compared with 29 postpartum healthy controls (HCs). Significant changes in protein intensities were determined with nonpaired Student's t-tests and were further classified by using the Boruta algorithm. The proteins' diagnostic performance was evaluated by area under the curve (AUC) and validated using the 10-fold cross-validation.Patients with PPCM presented with a mean left ventricular ejection fraction of 33.5% ± 9.3% vs 57.0% ± 8.8% in HCs (P < 0.001). Study investigators identified 15 differentially up-regulated and 14 down-regulated proteins in patients with PPCM compared with HCs. Seven of these proteins were recognized as significant by the Boruta algorithm. The combination of adiponectin, quiescin sulfhydryl oxidase 1, inter-α-trypsin inhibitor heavy chain, and N-terminal pro-B-type natriuretic peptide had the best diagnostic precision (AUC: 0.90; 95% CI: 0.84-0.96) to distinguish patients with PPCM from HCs.Salient biologic themes related to immune response proteins, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation were predominant in patients with PPCM compared with HCs. These newly identified proteins warrant further evaluation to establish their role in the pathogenesis of PPCM and potential use as diagnostic markers.
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