The role of CD147 N-glycosylation and IgG N-glycosylation in the inflammatory modulation of atherogenesis

Author Identifier

Cuihong Tian

Date of Award


Document Type

Thesis - ECU Access Only


Edith Cowan University

Degree Name

Doctor of Philosophy


School of Medical and Health Sciences

First Supervisor

Wei Wang

Second Supervisor

Xuerui Tan

Third Supervisor

Xingang Li

Fourth Supervisor

Chris Abbiss


Atherosclerosis, an immunoinflammatory cardiovascular disease progressing with ageing, is the leading cause of death globally. Research demonstrates that cluster of differentiation 147 (CD147) and immunoglobulin G (IgG) in blood are closely associated with the development of atherosclerosis. In addition, glycosylation has been demonstrated to be involved with inflammatory and ageing-related diseases, such as atherogenesis. However, the influences of glycosylated CD147 and glycosylated IgG on atherosclerosis in Han Chinese populations has yet to be investigated. Therefore, this PhD thesis aims to explore the potential role of CD147 Nglycosylation and IgG N-glycosylation on the development and progression of atherosclerosis, as demonstrated in the following four studies.

Study I. Bioinformatics of atherosclerosis: The microarray dataset GSE43292, including 32 carotid plaque tissues and 32 paired adjacent macroscopically intact tissues, was downloaded from the Gene Expression Omnibus database, and analysed to identify differentially expressed genes associated with carotid atherosclerosis (CAS). Their functional roles and interactions were then annotated and evaluated via Gene Ontology enrichment, the Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses. Matrix metallopeptidase 9 (MMP9) was found to be the hub gene most associated with CAS, indicating that CD147, as an agonist of MMP9, is associated with CAS.

Study II. Difference of CD147 N-glycosylation: Study II, designed as a propensity scorematched case-control study, was a subset extracted from the existing umbrella cohort (Health Examination Cohort Study, registration number: ChiCTR2100048740), which was carried out at the Health Care Centre in the First Affiliated Hospital of Shantou University Medical College, China, from August 1, 2021 to July 31, 2022. A total of 138 participants (69 CAS cases and 69 healthy controls) aged 50-65 years were retrospectively analysed to investigate the differences of CD147 protein and CD147 N-glycosylation expression patterns between CAS and controls among Han Chinese populations, which were examined by enzyme-linked immune sorbent assay. The profiling of CD147 N-glycosylation within cases was significantly higher than that in controls, although the expression of CD147 protein itself was not, indicating that CD147 N-glycosylation modification contributes to the pathophysiology of atherosclerosis.

Study III. Diagnostic performance of CD147 N-glycosylation: A retrospective study totalling 583 participants aged 50-65 years, extracted from the existing umbrella Health Examination Cohort Study, was conducted. Receiver operator characteristic (ROC) curve analysis was applied to calculate the optimal cut-off value of CD147 N-glycosylation for grouping (GlyCD147 < 1.81 group, n=271 and GlyCD147 ≥ 1.81 group, n=312). Multivariable logistic analyses were used to evaluate the association between CD147 N-glycosylation and CAS. The performance of CD147 N-glycosylation in diagnosing CAS was then evaluated by ROC curve analysis. The study indicated that: (i) CD147 N-glycosylation was an independent risk factor for CAS; (ii) both CD147 N-glycosylation itself and the model Y = -1.204 × female (yes) + 0.205 × age (years) + 1.261 × smoking (yes) + 3.070 × GlyCD147 ≥ 1.81 ug/l (yes) were excellent in predicting CAS; and (iii) the incidence of CAS in females was lower than that in males, indicating that the protective effect of estrogen on women with CAS aged from 50 to 65 years still exists, even though those females have entered menopause.

Study IV. Difference of IgG N-glycan profiles: This was also designed as a propensity score-matched case-control study. A sub-analysis of datasets among 138 participants aged 50-65 years, including 69 CAS patients and 69 healthy controls extracted from an existing umbrella of the Health Examination Cohort Study, was conducted to investigate the differences of IgG Nglycan profiles between CAS and controls. Fasting blood samples from participants were retrospectively analysed for whole serum IgG N-glycans profiling by Ultra-Performance Liquid Chromatography. The relative abundance of IgG fucosylation in CAS, i.e., F n , FG2 n n / G2 , and n F n / (B + FB n ), was significantly lower than that in controls. The thesis demonstrates that two inflammatory biomarkers, CD147 N-glycosylation and IgG N-glycosylation, are involved in the inflammatory modulation of atherogenesis. Future functional studies are required to explore the potential signalling pathway mechanism of these biomarkers in atherogenesis.



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