Screening differentially expressed proteins of coronary heart disease with congenital cold syndrome based on tandem mass tag (TMT) technology

ABSTRACT

In our previous studies, we discovered the congenital cold syndrome (CCS), which is characterized by ‘qi deficiency and qi stagnation, mixed cold and heat.’ And there is a type of syndrome with special incidence characteristic. However, the diagnosis of CCS still lacks an objective basis. In this study, we performed Tandem Mass Tag (TMT) based on quantitative proteomics technology to screen the significantly differentially expressed proteins (DEPs) in serum of patients with coronary heart disease (CHD) patients with CCS, patients with heart and kidney yang deficiency, and healthy people. A total of 22 DEPs (nine upregulated and 13 downregulated) were identified between patients with CCS and healthy subjects. Next, we performed GO and KEGG pathway enrichment analysis, we found the primary functions of DEPs of CCS were binding, catalytic activity, and molecular function regulator. These DEPs were mainly involved in important biological processes, such as cellular process, response to stimulus, localization, metabolic process, and biological regulation. The KEGG analysis revealed that the DEPs showed significant changes in fructose and mannose metabolism, Pentose phosphate pathway, and Arrhythmogenic right ventricular cardiomyopathy. After parallel reaction monitoring (PRM) verification, four upregulated target proteins (ALDOA, PCYOX1, Crisp3 and IGLV4-69) and three downregulated proteins (ALDOC, ADAMTSL-2 and C3) were accurately identified. These proteins were mainly related to immune response and glucose metabolism. These DEPs could be the marker proteins of coronary heart disease with CCS. This findings help to reveal the pathogenesis of CHD with CCS and provide potential therapeutic targets.

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KEYWORDS:

• Congenital cold syndrome
• proteome
• differentially expressed proteins

Highlights

1. Four upregulated target proteins (ALDOA, PCYOX1, Crisp3 and IGLV4-69) and three downregulated proteins (ALDOC, ADAMTSL-2 and C3) were accurately identified in CCS patients.

2. The primary functions of DEPs of CCS were binding, catalytic activity, and molecular function regulator.

3. The DEPs showed significant changes in fructose and mannose metabolism, Pentose phosphate pathway, and Arrhythmogenic right ventricular cardiomyopathy.

Abbreviations

CCS congenital cold syndrome

CHD coronary heart disease

DEPs differentially expressed proteins

TMT Tandem Mass Tag

TCM traditional Chinese medicine

HKYAD Patients with heart-kidney yang deficiency

GO Gene Ontology

KEGG Kyoto Encyclopedia of Genes and Genomes

PRM parallel reaction monitoring

ALDOA fructose-bisphosphate aldolase A

PCYOX1 prenylcysteine oxidase 1

Crisp3 cysteine-rich secretory protein 3

IGLV4-69 immunoglobulin lambda variable 4-69

ALDOC fructose-bisphosphate aldolase C

ADAMTSL-2 ADAMTS-like protein 2

C3 complement 3.

Acknowledgements

Thanks to the National Natural Science Foundation of China for funding this project. Thanks to Shanghai applied protein Technology Co., Ltd. for its technical support for this project.

Disclosure statement

No potential conflict of interest was reported by the author(s).