Integrated plasma and vegetation proteomic characterization of infective endocarditis for early diagnosis and treatment

Shiman He, Xuejiao Hu, Jiajun Zhu, Weiteng Wang, Chi Ma, Peng Ran, Oudi Chen, Fanyu Chen, Hongkun Qing, Jianhong Ma, Danni Zeng, Yunzhi Wang, Weijiang Liu, Jinwen Feng, Lixi Gan, Zhaoyu Qin, Subei Tan, Sha Tian, Chen Ding (), Xuhua Jian () and Bing Gu ()
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Shiman He: Fudan University
Xuejiao Hu: Southern Medical University
Jiajun Zhu: Fudan University
Weiteng Wang: Southern Medical University
Chi Ma: Fudan University
Peng Ran: Fudan University
Oudi Chen: Southern Medical University
Fanyu Chen: Southern Medical University
Hongkun Qing: Southern Medical University
Jianhong Ma: Heyuan People’s Hospital
Danni Zeng: Southern Medical University
Yunzhi Wang: Fudan University
Weijiang Liu: Southern Medical University
Jinwen Feng: Fudan University
Lixi Gan: Southern Medical University
Zhaoyu Qin: Fudan University
Subei Tan: Fudan University
Sha Tian: Fudan University
Chen Ding: Fudan University
Xuhua Jian: Southern Medical University
Bing Gu: Southern Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract Infective endocarditis, a life-threatening condition, poses challenges for early diagnosis and personalized treatment due to insufficient biomarkers and limited understanding of its pathophysiology. Here, we performed proteomic profiling of plasma and vegetation samples from 238 patients with infective endocarditis and 100 controls, with validation in two external plasma cohorts (n = 328). We developed machine learning-based diagnostic and prognostic models for infective endocarditis, with area under the curve values of 0.98 and 0.87, respectively. Leucine-rich alpha-2-glycoprotein 1 and NADH:ubiquinone oxidoreductase subunit B4 are potential biomarkers associated with infection severity. Pathologically, protein networks characterized by glycometabolism, amino acid metabolism, and adhesion are linked to adverse events. Liver dysfunction may exacerbate the condition in patients with severe heart failure. Neutrophil extracellular traps emerge as promising therapeutic targets in Streptococcus or Staphylococcus aureus infections. Our findings provide insights into biomarker discovery and pathophysiological mechanisms in infective endocarditis, advancing early diagnosis and personalized medicine.

Date: 2025
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DOI: 10.1038/s41467-025-60184-8

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