Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling.

Varicose veins are a prevalent vascular disorder affecting millions of individuals worldwide, and we previously reported transfer RNA-derived fragment (tRF) involvement in varicose veins. This study investigated the role of tRF-36 in varicose vein pathogenesis. Varicose veins and adjacent normal vascular tissues were collected to measure the expression of Notch 1, 2, and 3 and the smooth muscle cell (SMC) markers SMA-α, and SM22α. Human vascular SMCs (HVSMCs) were transfected to alter tRF-36 levels and examine the effects on Notch 1-3, tRF-36, SMA-α, and SM22α expression. Notch 1-3 and tRF-36 levels were higher in varicose veins than in adjacent normal vascular tissues. tRF-36 knockdown decreased HVSMC viability, downregulated Notch 1, 2, and 3 expression, and upregulated SMC markers (SMA-α and SM22α) compared with control HVSMCs. When the Notch pathway was inhibited, the expression of tRF-36 was significantly reduced. Additionally, Notch pathway inhibition showed similar effects to tRF-36 knockdown on HVSMC viability and the expression of SMA-α and SM22α. Furthermore, a Notch pathway inhibitor reversed the effects of the tRF-36 mimic on HVSMCs. Our study suggests a critical role for tRF-36 in varicose veins and demonstrates that tRF-36 knockdown may suppress varicose vein progression by inhibiting the Notch signaling pathway.