[P005] Poster

12:10 PM - 1:00 PM JST(3:10 AM - 4:00 AM UTC)

[P03-375] Blood Reflux-Induced microRNAs Are Associated with the Development of Human Venous Disease

○Ting Yu Lee¹ (1. National Taiwan Ocean University (Taiwan))

Keywords:

miRNA,venous disease

[Purpose] MicroRNAs (miRNAs) have emerged as vital modulators of vascular function and dysfunction. Hemodynamic flow patterns, such as laminar or oscillatory flow, have also been shown to regulate endothelial cell (EC) homeostasis. This study aimed to determine the roles of miRNAs in venous ECs in response to blood reflux and to correlate these factors with the development of chronic venous disease (CVD).

[Method] Using in vivo human studies and in vitro flow experiments, we examined the role of blood reflux in modulating miRNA signaling.

[Results] We found that the expression of pathogenic miRNAs (i.e., inflammatory miR-92a and miR-663) was upregulated in the endothelium of human CVD veins exhibiting blood reflux, whereas protective miRNAs (i.e., anti-inflammatory miR-10a and vascular repair-associated miR-126-5p) were downregulated. Furthermore, we demonstrated that blood reflux-induced oscillatory flow plays a major role in driving the overexpression of inflammatory GATA6 and anti-proliferative DLK1, alongside the suppression of anti-inflammatory KLF4 and KLF2 in venous ECs. In vitro transfection of venous ECs with precursor miRNAs (miR-10a or miR-126-5p) or antagomiRs (miR-663 or miR-92a) abolished this blood reflux-induced pathogenic signaling.

[Conclusion] The results indicate that miRNA expression is significantly altered in the endothelium of human CVD veins subjected to blood reflux, thereby mediating pathogenic signaling related to inflammation and cellular turnover imbalance. Consequently, the targeted manipulation of miRNA expression holds significant potential as a novel therapeutic strategy for human CVD.