Speakers - DEWC2025

Abstract

Background
Diabetic cardiovascular complications, encompassing both microvascular and macrovascular disorders, are major contributors to morbidity and mortality in diabetes. Dietary fatty acids significantly influence these outcomes. While the effects of saturated (SFAs) and unsaturated fatty acids (UFAs) remain debated, emerging evidence suggests that moderate intake of certain trans-fatty acids (TFAs) may benefit cardiovascular health. However, specific TFAs, such as elaidic acid (EA), have been associated with worsening diabetic vascular damage. The underlying molecular mechanisms remain unclear. This study aims to explore how EA contributes to diabetic cardiovascular complications and to identify key genes and pathways involved in its vascular toxicity.

Methods
We employed network toxicology, bioinformatics, and molecular docking analyses. Public databases were used to identify EA-related targets and pathways relevant to diabetic cardiovascular disease. Molecular docking assessed the binding affinity between EA and core protein targets. Target relevance under diabetic conditions was validated using the Attie Lab Diabetes Database.

Results
We identified 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) as a key molecular target of EA. Docking analysis further suggested that EA activates HMGCR directly, rather than through sterol regulatory element-binding protein 2 (SREBP2).

Conclusion
Our findings highlight a potential pathogenic role of EA in diabetic vascular complications through direct activation of HMGCR and enhanced cholesterol synthesis.