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CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm

Eun Na Kim, Jiyoung Yu, Joon Seo Lim, Hwangkyo Jeong, Chong Jai Kim, Jae-Sung Choi, So Ra Kim, Hee-Sung Ahn, Kyunggon Kim, View ORCID ProfileSe Jin Oh
doi: https://doi.org/10.1101/2020.12.30.424789
Eun Na Kim
1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Jiyoung Yu
2Clinical Proteomics Core Lab, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Joon Seo Lim
3Clinical Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Hwangkyo Jeong
2Clinical Proteomics Core Lab, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Chong Jai Kim
1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Jae-Sung Choi
4Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea
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So Ra Kim
3Clinical Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Hee-Sung Ahn
2Clinical Proteomics Core Lab, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Kyunggon Kim
2Clinical Proteomics Core Lab, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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  • For correspondence: sejinoh3@gmail.com kimkyunggon@gmail.com
Se Jin Oh
4Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea
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  • ORCID record for Se Jin Oh
  • For correspondence: sejinoh3@gmail.com kimkyunggon@gmail.com
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Abstract

Objective The molecular mechanisms of the degeneration of the aortic wall in abdominal aortic aneurysm (AAA) are poorly understood. The monomeric form of C-reactive protein (mCRP) is deposited in damaged cardiovascular organs and aggravates the prognosis; however, it is unknown whether mCRP is deposited in the degenerated aorta of abdominal aortic aneurysm (AAA). We investigated whether mCRP is deposited in AAA and examined the associated pathogenic signaling pathways.

Methods Twenty-four cases of AAA were analyzed and their histological features were compared according to the level of serum CRP and the degree of mCRP deposition. Proteomic analysis was performed in AAA cases with strong and diffuse CRP immunopositivity (n=7) and those with weak, focal, and junctional CRP immunopositivity (n=3).

Results mCRP was deposited in the aortic specimens of AAA in a characteristic pattern that coincided with the lesion of the diminished elastic layer of the aortic wall. High serum CRP level was associated with stronger mCRP immunopositivity and a larger maximal diameter of aortic aneurysm. Proteomic analysis in AAA showed that multiple proteins were differentially expressed according to mCRP immunopositivity. Also, ingenuity pathway analysis showed that pathways associated with atherosclerosis, acute phase response, complement system, immune system, and coagulation were enriched in AAA cases with high mCRP immunopositivity.

Conclusions AAA showed a characteristic deposition of mCRP, and multiple potentially pathologic signaling pathways were upregulated in AAA cases with strong CRP immunopositivity. mCRP and the aforementioned pathological pathways may serve as targets for managing the progression of AAA.

  • Abbreviations

    AAA
    abdominal aortic aneurysm
    AAA-high mCRP
    abdominal aortic aneurysm with strong and diffuse mCRP immunopositivity
    AAA-low mCRP
    abdominal aortic aneurysm with weak, focal and junctional mCRP immunopositivity
    AAD
    ascending aortic dissection
    CRP
    C-reactive protein
    DEPs
    differentially expressed proteins
    FDR
    false discovery rate
    FFPE
    formalin-fixed paraffin-embedded
    FKBP2
    FK506-binding protein 2
    H&E
    hematoxylin and eosin
    hsCRP
    high sensitive C-reactive protein
    IPA
    ingenuity pathway analysis
    IRB
    institutional review board
    LC-MS/MS
    liquid chromatography with tandem mass spectrometry
    LXR/RXR
    liver X receptor/retinoid X receptor
    MCP-1
    monocyte chemoattractant protein-1
    mCRP
    monomeric form of C-reactive protein
    MMPs
    matrix metalloproteinases
    PCA
    principal component analysis
    pCRP
    pentameric form of C-reactive protein
    WBC
    white blood cell count
  • Copyright 
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    Posted December 30, 2020.
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    CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm
    Eun Na Kim, Jiyoung Yu, Joon Seo Lim, Hwangkyo Jeong, Chong Jai Kim, Jae-Sung Choi, So Ra Kim, Hee-Sung Ahn, Kyunggon Kim, Se Jin Oh
    bioRxiv 2020.12.30.424789; doi: https://doi.org/10.1101/2020.12.30.424789
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    CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm
    Eun Na Kim, Jiyoung Yu, Joon Seo Lim, Hwangkyo Jeong, Chong Jai Kim, Jae-Sung Choi, So Ra Kim, Hee-Sung Ahn, Kyunggon Kim, Se Jin Oh
    bioRxiv 2020.12.30.424789; doi: https://doi.org/10.1101/2020.12.30.424789

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