The circulating heat shock proteins as a systems biomarker for coronary artery disease

Heat Shock Proteins (HSPs) have essential roles in cellular stress responses and have emerging clinical relevance in cardiovascular diseases, including coronary artery disease (CAD). Understanding their evolutionary relationships, expression patterns, and diagnostic value is crucial for CAD research. In this study, we investigated five key human HSPs (HSP27, HSP40, HSP60, HSP70 and HSP90), combining phylogenetic analysis with expression profiling and diagnostic evaluation. Phylogenetic relationship was inferred using the Neighbor-joining method. Additionally, the expression profiles of these HSPs were assessed at mRNA and protein levels. Groupwise correlation among HSPs was visualised as correlation matrices, and multivariate analysis confirmed a significant difference between CAD and controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic potential. Phylogenetic analysis revealed two closely related subfamily pairs (HSP60-HSP70 and HSP40-HSP90), each forming a separate cluster. HSP27, in contrast, displayed divergence, branching separately from the other HSPs. Expression studies showed significant upregulation in the HSP40, HSP60, HSP70 and HSP90 expression; however, HSP27 shows downregulation in CAD patients compared to controls. In controls, inter-HSP correlations were predominantly positive, especially among HSP27, HSP40, and HSP90. In CAD, the HSP40-HSP90 axis remained strongly positive, whereas HSP90-HSP27 and HSP27-HSP40 were disrupted and weak, indicating disease-associated rewiring of the chaperone network. ROC curve shows the predictive power, with AUC values of 0.97 for HSP40 and HSP60, and 0.92 for HSP70 and HSP90, supporting their utility as potential biomarkers for CAD. These findings highlight both the conserved functional relevance and clinical value of HSP chaperones in CAD.