An Association Between GLP-1 Receptor Expression on Regulatory T Cells and the Severity of Coronary Artery Stenosis and Inflammatory Dysregulation in Coronary Heart Disease.

BACKGROUND

Regulatory T cells (Tregs) play pivotal roles in immune homeostasis; however, the association between Tregs and the pathogenesis of coronary heart disease (CHD) remains unclear. Thus, this study aimed to investigate the relationships among Tregs, glucagon-like peptide-1 receptor (GLP-1R) expression, and CHD risk, with a focus on the severity of coronary artery stenosis and inflammatory cytokine dynamics.

METHODS

A total of 130 CHD patients (stratified by the Gensini score into low-/high-risk stenosis subgroups) and 70 non-CHD controls were enrolled in this case-control study. Peripheral blood Tregs (CD4+CD25+FoxP3+) and GLP-1R+ Tregs were quantified via flow cytometry. Plasma cytokines interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-35 (IL-35), and tumor necrosis factor-alpha (TNF-α) were measured. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were employed to evaluate the associations between Treg subsets and clinical outcomes; meanwhile, the Spearman correlation was used to assess the relationships between cytokines.

RESULTS

CHD patients presented with significantly lower proportions of total Tregs (p < 0.001) and GLP-1R+ Tregs (p = 0.013) compared to controls, with further reductions in the high-risk stenosis subgroups. Multivariate analysis identified both Tregs (CHD: odds ratio (OR) = 0.752; p < 0.001; stenosis: OR = 0.760; p = 0.021) and GLP-1R+ Tregs (CHD: OR = 0.859; p = 0.013; stenosis: OR = 0.840; p = 0.040) as independent predictors. The ROC analysis demonstrated diagnostic utility for Tregs (CHD: area under the curve (AUC) = 0.663; stenosis: AUC = 0.635) and GLP-1R+ Tregs (CHD: AUC = 0.600; stenosis: AUC = 0.619). The GLP-1R+ Treg proportion was positively correlated with anti-inflammatory IL-35 (r = 0.185, p = 0.016) and inversely correlated with IL-4 (r = -0.150, p = 0.047).

CONCLUSION

Reduced Treg frequency and impaired GLP-1R expression on Tregs are independently associated with CHD susceptibility and stenosis progression, potentially mediated by dysregulation of inflammatory cytokines. The GLP-1R pathway in Tregs represents a novel immunomodulatory target for therapeutic intervention in CHD.