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

Journal: Nature communications
Published Date: May 30, 2025

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.

Authors

  • Shiman He
    Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Xuejiao Hu
    School of Information Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.
  • Jiajun Zhu
    Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China.
  • Weiteng Wang
    Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Chi Ma
    Department of Radiation Oncology, Rutgers-Cancer Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, United States.
  • Peng Ran
    Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Oudi Chen
    Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Fanyu Chen
    Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Hongkun Qing
    Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Jianhong Ma
    Department of Laboratory Medicine, Heyuan People's Hospital, Heyuan, China.
  • Danni Zeng
    Department of Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Yunzhi Wang
    School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK, USA.
  • Weijiang Liu
    Department of Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Jinwen Feng
    Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
  • Lixi Gan
    Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Zhaoyu Qin
    Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Subei Tan
    Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Sha Tian
    Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Chen Ding
    Department of Cardiology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, Jiangsu, China.
  • Xuhua Jian
    Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. jianxuhua@gdph.org.cn.
  • Bing Gu
    Laboratory Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China.

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