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Background <p>Atherosclerosis is an inflammatory cardiovascular disease that progresses with ageing. Glycosylation plays a significant role in inflammation and contributes to the pathogenesis of ageing-related diseases, including atherosclerosis. Cluster of differentiation 147 (CD147), a glycosylated agonist of matrix metallopeptidase 9 (MMP9), serves as an inducer of atherosclerosis and atherothrombosis. However, the effect of glycosylated CD147 (GlyCD147) on atherosclerosis remains unclear. This research aims to identify whether GlyCD147 is associated with atherosclerosis.</p> Methods <p>To begin with, a clinical case-control study was designed to assess the differences of CD147 and GlyCD147 between 69 carotid atherosclerosis (CAS) cases and 69 controls. Traditional atherosclerotic risk factors, including age, gender, smoking, alcohol consumption, hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia and obesity, between cases and controls were matched by propensity score matching. Next, a cross-sectional study including 583 participants was conducted to confirm the association of GlyCD147 with CAS by multivariable logistic analysis, which was further examined within subgroups defined by age, gender, smoking, hypertension, T2DM and dyslipidemia. Subsequently, the differentially expressed key genes of carotid artery atheroma were identified by profiling the GSE43292 gene expression dataset.</p> Results <p>The serum level of GlyCD147 in CAS cases was higher than that in controls [2.40&#xa0;µg/L vs. 1.06&#xa0;µg/L, <i>P</i> &lt; 0.001], whereas no significant difference of CD147 protein level was observed. Elevated GlyCD147 was positively associated with risk of CAS (adjusted odds ratio 21.57, 95% confidence interval 13.10-35.52, <i>P</i> &lt; 0.001). Especially, GlyCD147 was shown to raise risk of CAS onset across different subgroups. The top hub gene associated with CAS was MMP9 based on its high degree centrality in protein-protein interaction network, which was upregulated in atheroma plaques in comparison to the adjacent tissues.</p> Conclusion <p>This research demonstrated that GlyCD147 is independently associated with CAS even with other traditional atherosclerotic risk factors being considered. A potential pathogenesis underlying this association could be that GlyCD147 may be involved in CAS by promoting an MMP9-mediated inflammatory response, a hypothesis that warrants future validation through functional experiments.</p>

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Association of GlyCD147 with carotid atherosclerosis: evidence from integrative analyses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月28日

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  • Cuihong Tian,
  • Peixuan Yang,
  • Xingang Li,
  • Hongxia Zhang,
  • Jieyi He,
  • Jinxiu Zhu,
  • Yequn Chen,
  • Xuerui Tan

摘要

Background

Atherosclerosis is an inflammatory cardiovascular disease that progresses with ageing. Glycosylation plays a significant role in inflammation and contributes to the pathogenesis of ageing-related diseases, including atherosclerosis. Cluster of differentiation 147 (CD147), a glycosylated agonist of matrix metallopeptidase 9 (MMP9), serves as an inducer of atherosclerosis and atherothrombosis. However, the effect of glycosylated CD147 (GlyCD147) on atherosclerosis remains unclear. This research aims to identify whether GlyCD147 is associated with atherosclerosis.

Methods

To begin with, a clinical case-control study was designed to assess the differences of CD147 and GlyCD147 between 69 carotid atherosclerosis (CAS) cases and 69 controls. Traditional atherosclerotic risk factors, including age, gender, smoking, alcohol consumption, hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia and obesity, between cases and controls were matched by propensity score matching. Next, a cross-sectional study including 583 participants was conducted to confirm the association of GlyCD147 with CAS by multivariable logistic analysis, which was further examined within subgroups defined by age, gender, smoking, hypertension, T2DM and dyslipidemia. Subsequently, the differentially expressed key genes of carotid artery atheroma were identified by profiling the GSE43292 gene expression dataset.

Results

The serum level of GlyCD147 in CAS cases was higher than that in controls [2.40 µg/L vs. 1.06 µg/L, P < 0.001], whereas no significant difference of CD147 protein level was observed. Elevated GlyCD147 was positively associated with risk of CAS (adjusted odds ratio 21.57, 95% confidence interval 13.10-35.52, P < 0.001). Especially, GlyCD147 was shown to raise risk of CAS onset across different subgroups. The top hub gene associated with CAS was MMP9 based on its high degree centrality in protein-protein interaction network, which was upregulated in atheroma plaques in comparison to the adjacent tissues.

Conclusion

This research demonstrated that GlyCD147 is independently associated with CAS even with other traditional atherosclerotic risk factors being considered. A potential pathogenesis underlying this association could be that GlyCD147 may be involved in CAS by promoting an MMP9-mediated inflammatory response, a hypothesis that warrants future validation through functional experiments.