State-Dependent DNA Methylation Signatures Distinguish Acute from Stable Coronary Syndromes.

Unsupervised hierarchical clustering revealed clear separation between ACS, SCS, and control samples, indicating distinct epigenetic profiles.

• Genome-wide DNA methylation analysis was performed using pairwise comparisons: ACS vs. control, SCS vs. control, and ACS vs. SCS.
• Differentially methylated regions were identified using logistic regression implemented in the methylKit package in R.
• Regions were considered significant with a false discovery rate-adjusted q-value < 0.05 and an absolute methylation difference (|Δβ|) > 20%.
• The separation was described as 'clear,' suggesting robust epigenetic distinction between all three groups.

ACS showed the most pronounced methylation alterations compared to controls, whereas SCS exhibited more moderate changes consistent with chronic epigenetic remodeling.

• Both ACS and SCS were compared independently against healthy controls.
• ACS methylation changes were described as the most pronounced of the two disease states.
• SCS changes were characterized as 'moderate' and consistent with chronic, rather than acute, epigenetic remodeling.
• This pattern suggests a gradient of epigenetic disruption corresponding to disease acuity.

Direct comparison between ACS and SCS identified dynamic, state-dependent methylation differences.

• A dedicated pairwise comparison of ACS vs. SCS was performed in addition to comparisons against healthy controls.
• The differences were described as 'dynamic' and 'state-dependent,' indicating they are not simply a continuum but reflect distinct disease states.
• These differences were identified using the same significance thresholds: FDR-adjusted q-value < 0.05 and |Δβ| > 20%.

Pathway analysis demonstrated enrichment of stress response, apoptotic signaling, and cell adhesion pathways specifically in ACS.

• Pathway enrichment analysis was conducted on differentially methylated regions identified in ACS versus controls.
• Enriched pathways in ACS included stress response, apoptotic signaling, and cell adhesion pathways.
• These pathways were interpreted as potentially contributing to acute plaque destabilization.
• The enrichment pattern was distinct from that observed in SCS.

SCS was primarily associated with pathways related to intercellular communication and vascular signaling in pathway analysis.

• Pathway enrichment analysis was conducted on differentially methylated regions identified in SCS versus controls.
• Enriched pathways in SCS included intercellular communication and vascular signaling.
• These pathways were interpreted as consistent with chronic disease progression rather than acute events.
• The SCS pathway signature was distinct from the stress response and apoptotic pathways enriched in ACS.

DNA methylation was highlighted as a potential molecular marker in coronary artery disease for distinguishing disease acuity.

• The study concludes that epigenetic regulation of stress, adhesion, and signaling pathways may contribute to disease acuity and progression.
• The authors propose DNA methylation as a 'potential molecular marker in coronary artery disease.'
• The findings suggest that genome-wide methylation profiling can differentiate not only disease from health but also acute from stable disease states.
• The study used pairwise comparisons across three groups: ACS patients, SCS patients, and healthy controls.