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Data-Independent Acquisition-Based Serum Proteomic Profiling of Adult Moyamoya Disease Patients Reveals the Potential Pathogenesis of Vascular Changes

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Abstract

Moyamoya disease (MMD) is a chronic cerebrovascular disease with unknown etiology. The pathogenesis of vascular changes remains unclear. Ischemic and hemorrhagic adult MMD patients and healthy volunteers were enrolled to collect serum for data-independent acquisition (DIA)-based proteomic analysis and ELISA validation. DIA serum proteomic revealed that apolipoprotein C-I (APOC1), apolipoprotein D (APOD), and apolipoprotein A-IV (APOA4) were decreased. The reductases glutathione S-transferase omega-1 (GSTO1) and peptidyl-prolyl cis–trans isomerase A (PPIA) were upregulated, and ADAMTS-like protein 4 (ADAMTSL4) was downregulated in both ischemic and hemorrhagic MMD. Afamin (AFM) and transforming growth factor-beta-induced protein ig-h3 (TGFBI) increased in ischemic patients but decreased in hemorrhagic patients. Serum ELISA results confirmed that APOA4, APOC1, and APOD were decreased compared to controls. Then, we retrospectively analyzed biochemical indexes of 200 MMD patients. A total of 54 enrolled MMD patients showed decreased total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-c). APOA4, APOC1, and APOD were vital factors in the HDL decrease in MMD patients. Lipoprotein dysfunction in MMD patients is involved in MMD. Intimal thickening by enhanced adhesion, middle layer vascular smooth muscle cell migration, and decreased lipid antioxidant function represented by HDL are potential pathogeneses of vascular changes in MMD.

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Data Availability

Datasets of proteomics analyses and other material related to the current study are readily available upon request.

Code Availability

Not applicable.

Abbreviations

MMD:

Moyamoya disease

MMS:

Moyamoya syndrome

DIA:

Data-independent acquisition

LC–MS/MS:

Liquid chromatography-tandem mass spectrometry

FDR:

False discovery rate

KEGG:

Kyoto Encyclopedia of Genes and Genomes

GO:

Gene Ontology

PCA:

Principal component analysis

APOC1:

Apolipoprotein C-I

APOD:

Apolipoprotein D

APOA4:

Apolipoprotein A-IV

GSTO1:

Glutathione S-transferase omega-1

PPIA:

Peptidyl-prolyl cis–trans isomerase A

ADAMTSL4:

ADAMTS-like protein 4

AFM:

Afamin

TGFBI:

Transforming growth factor-beta-induced protein ig-h3

TC:

Total cholesterol

TG:

Triglycerides

HDL:

High-density lipoprotein

VHDL:

Very-low-density lipoprotein

LDL:

Low-density lipoprotein

VLDL:

Very-low-density lipoprotein

LCAT:

Lecithin cholesterol acyltransferase

LFA-1:

Lymphocyte function-associated antigen 1

VSMCs:

Vascular smooth muscle cells

ICAM:

Intercellular adhesion molecule

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Funding

This work was supported by the National Natural Science Foundation of China (NSFC) grant (82002643), Postdoctoral Research Foundation of China grant (2019M651954), and Gusu Health Personal Training Project (GSWS2019002).

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Author notes

  1. Zongqi Wang, Chengyuan Ji, and Qingdong Han contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, 188 Shizi Street, Suzhou, 215006, China

    Zongqi Wang, Chengyuan Ji, Qingdong Han, Zhong Wang & Yabo Huang

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  1. Zongqi Wang
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  4. Zhong Wang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Zongqi Wang, Chengyuan Ji, and Qingdong Han. The first draft of the manuscript was written by Zongqi Wang. Writing—review and editing by Qingdong Han and Yabo Huang. Funding acquisition: Zongqi Wang and Zhong Wang. Supervision: Zhong Wang. All authors read and approved the final manuscript.

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Correspondence to Zhong Wang or Yabo Huang.

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All individual participants enrolled in this study were informed of the trial and signed an informed consent form. This study was performed following the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the ethics committee of the First Affiliated Hospital of Soochow University.

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Wang, Z., Ji, C., Han, Q. et al. Data-Independent Acquisition-Based Serum Proteomic Profiling of Adult Moyamoya Disease Patients Reveals the Potential Pathogenesis of Vascular Changes. J Mol Neurosci 72, 2473–2485 (2022). https://doi.org/10.1007/s12031-022-02092-w

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