Reduced circulating 20-hydroxyeicosatetraenoic acid and ACE2 in acute coronary syndrome with exploratory cell-based observations

Figures

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  Fig. 1. Distribution of circulating ACE2 and 20-HETE levels across the study groups. Individual data points are shown for ACE2 (a) and 20-HETE (b) concentrations in the comparison, SCAD, and ACS groups. Horizontal lines and error bars indicate medians with interquartile ranges. Differences between two groups were assessed using the Mann–Whitney U test with Bonferroni correction following an overall Kruskal–Wallis test. p-values shown above the plots indicate significant pairwise comparisons. Effect sizes are presented as median differences between groups: for ACE2, comparison vs. ACS Δmedian = 2.46 ng/mL and SCAD vs. ACS Δmedian = 1.75 ng/mL; for 20-HETE, comparison vs. ACS Δmedian = 46.53 ng/mL and SCAD vs. ACS Δmedian = 21.07 ng/mL. 20-HETE – 20-hydroxyeicosatetraenoic acid; ACE2 – angiotensin-converting enzyme 2.

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  Fig. 2. Proposed model of ACE2/RAS–eicosanoid axis dysregulation in ACS. The schematic illustrates how dysregulation of the ACE2/RAS–eicosanoid signaling pathway contributes to ACS. A decline in ACE2 activity skews the RAS toward a pro-inflammatory and vasoconstrictive state, reducing NO availability and causing endothelial dysfunction. This imbalance leads to endothelial activation, with increased expression of adhesion molecules like ICAM-1 and VCAM-1. Additionally, changes in RAS signaling are linked to disrupted CYP4F2-dependent eicosanoid metabolism. In ACS, circulating 20-HETE levels are significantly decreased, possibly due to increased consumption or defective synthesis during acute inflammation and clot formation. At the cellular level, 20-HETE influences metabolic activity and activates GPR75 signaling, suggesting its role as an active lipid mediator rather than just a marker. Overall, these mechanisms form an interconnected ACE2/RAS–NO–inflammation–CYP4F2–20-HETE–GPR75 signaling network that links endothelial dysfunction to vascular instability and the onset of acute coronary events.